�Mammalian fatso acid synthase is peerless of the most building complex molecular synthetic machines in human cells. It is also a promising target for the development of anti-cancer and anti-obesity drugs and the treatment of metabolic disorders. Now researchers at ETH Zurich have determined the atomic structure of a mammalian fat person acid synthase. Their results have just been published in Science magazine.
Synthesis of fatty acids is a central cellular process that has been studied for many decades. Fatty acids are used in the cell as energy storage compounds, messenger molecules and building blocks for the cellular envelope. Until now, individual steps of this process have been investigated using separated bacterial enzymes. However, in higher organisms except plants fatty acidic synthesis is catalyzed by large multifunctional proteins where many item-by-item enzymes ar brought in concert to configuration a "molecular assembly line".
The atomic body structure is the result of many days of research
As described in this week's issue of "Science" magazine, researchers at ETH Zurich, supported by the National Centre of Excellence in Research (NCCR) in Structural Biology at the Swiss National Science Foundation, dictated the high-resolution structure of a mammalian fatty acrid synthase exploitation data gathered at the Swiss Light Source (SLS) of the Paul Scherrer Institute (PSI) in Switzerland. These results crown the efforts begun in 2001 to find the detailed structures of fatty caustic synthases in higher organisms by a relatively small group of scientists at ETH Zurich. The mathematical group, consisting of Timm Maier, Marc Leibundgut and Simon Jenni in the research laboratory of Prof. Nenad Ban, published their first written document describing architectures of fungous and mammal fatty acid synthases two years ago. That was followed last year by two document on the atomic structures of fungous fatty virulent synthases and the mechanism of substratum shuttling and delivery in these multi-enzymes. Now this latest publication describes the atomic social structure of the mammalian fatso acid synthase. These results reveal the details of all catalytic active sites responsible for iterative fatso acid deduction and shew how the flexibility of this large multi-enzyme is used for transferring substrates from one and only enzymatic active site to the next. The structure can be considered a milestone for future inquiry in the field.
Fatty acid synthases as drug targets?
In addition to the cardinal scientific involvement in the function of this multi-enzyme that plays a central role in primary metabolism, mammalian fat person acid synthase is as well considered a promising dose target. Although most fat accumulated in animals and humans is delivered to cells by ingestion and not by de novo synthesis, compounds that inhibit the occasion of the mammalian roly-poly acid synthase induce weight reduction in animals, showing potential for the treatment of corpulency and obesity-related diseases, such as diabetes and coronary thrombosis disorders. Furthermore, due to the increased requirement for fatty sulfurous synthesis in cancer cells, inhibitors of this enzyme have anticancer activity, making fatty acid synthase an attractive drug target for anti-cancer therapy.
Multi-enzymes: the ultimate organic chemists
Mammalian fatty acerbic synthase belongs to a large fellowship of multi-enzymes, some of which are responsible for the deductive reasoning of complex natural products with antibiotic, anti-cancer, antimycotic agent and immunosuppressor properties that are of outstanding medical relevance. The structure of mammalian fat person acid synthase reveals how different catalytic domains are excised or inserted in various members of this family to yield multi-enzymes capable of synthesizing a large variety of chemical products. The structure will facilitate the design of molecular assemblage lines for the production of improved compounds. In particular, the engineering of novel multi-enzymes for the production of modified antibiotics is important in the fight against resistant strains of bacteria.
ETH ZUERICH
Raemistrasse 101
CH - 8006 Zuerich
http://www.ethz.ch
More info
Tuesday, 9 September 2008
Saturday, 30 August 2008
Women May Stop Anticoagulants After Blood Clots
�Women may safely cease oral anticoagulants (blood thinners) after 6 months of treatment following a low gear unprovoked venous blood clog (thromboembolism) if they take no or one danger factor, concludes a survey of 646 participants in a multicentre prospective cohort study.
Blood clots are common and a potentially fatal condition. For patients with unwritten blood clots who stop anticoagulation therapy, the risk of exposure of a recurrence in the first base year is 5% to 27%, notwithstanding there is a risk of exposure of major bleeding and fatal hemorrhage while continuing anticoagulants.
"It may be safe for women wHO have taken oral anticoagulants for fifty-seven months after an motiveless venous thromboembolism to discontinue therapy if they have 0 or 1 of the next: 1) hyperpigmentation (brown discoloration), edema (prominence) or inflammation of either leg; 2) a D-dimer level (blood clotting test) of 250ug/L or more while taking warfarin, 3) BMI [body mass index] 30kg/m2; and aged 65 years or more," close Dr. Marc Rodger and coauthors.
The authors caution that "it appears all men are at highschool risk of recurrence" and further investigation into risk determination inevitably to be pursued.
In an resultant commentary, Dr. Clive Kearon states that patient preference for the duration of anticoagulant therapy must be considered in deciding whether to continue or discontinue therapy.
About CMAJ (Canadian Medical Association Journal)
CMAJ is the leading health sciences journal in Canada. CMAJ is a universal medical diary publishing original research and review articles, commentaries and editorials, practice updates, an arts and ideas section and health news. Published continuously since 1911, new issues are uploaded on http://www.cmaj.ca every arcsecond Monday at 4:30 p.m. EST/EDT. hypertext transfer protocol://www.cmaj.ca contains the finish editorial table of contents of CMAJ, supplemented by a variety of interactive features and additional content.
Canadian Medical Association Journal
View dose information on Warfarin Sodium tablets.
More information
Blood clots are common and a potentially fatal condition. For patients with unwritten blood clots who stop anticoagulation therapy, the risk of exposure of a recurrence in the first base year is 5% to 27%, notwithstanding there is a risk of exposure of major bleeding and fatal hemorrhage while continuing anticoagulants.
"It may be safe for women wHO have taken oral anticoagulants for fifty-seven months after an motiveless venous thromboembolism to discontinue therapy if they have 0 or 1 of the next: 1) hyperpigmentation (brown discoloration), edema (prominence) or inflammation of either leg; 2) a D-dimer level (blood clotting test) of 250ug/L or more while taking warfarin, 3) BMI [body mass index] 30kg/m2; and aged 65 years or more," close Dr. Marc Rodger and coauthors.
The authors caution that "it appears all men are at highschool risk of recurrence" and further investigation into risk determination inevitably to be pursued.
In an resultant commentary, Dr. Clive Kearon states that patient preference for the duration of anticoagulant therapy must be considered in deciding whether to continue or discontinue therapy.
About CMAJ (Canadian Medical Association Journal)
CMAJ is the leading health sciences journal in Canada. CMAJ is a universal medical diary publishing original research and review articles, commentaries and editorials, practice updates, an arts and ideas section and health news. Published continuously since 1911, new issues are uploaded on http://www.cmaj.ca every arcsecond Monday at 4:30 p.m. EST/EDT. hypertext transfer protocol://www.cmaj.ca contains the finish editorial table of contents of CMAJ, supplemented by a variety of interactive features and additional content.
Canadian Medical Association Journal
View dose information on Warfarin Sodium tablets.
More information
Sunday, 10 August 2008
Searing Meadow
Artist: Searing Meadow
Genre(s):
Metal: Death,Black
Discography:
Once Adored
Year: 2001
Tracks: 3
Mariah Carey spends 2.5 million on mansion
Tuesday, 1 July 2008
Potential Bad Boy
Artist: Potential Bad Boy
Genre(s):
Drum & Bass
Discography:
JHR001 DD
Year: 2005
Tracks: 2
Play It Kik It Ep RPG005 Viny
Year: 2004
Tracks: 4
Thursday, 19 June 2008
Encounter with Luna, the killer whale, is lesson in stewardship
In September 2005, I accompanied two Mowachaht/Muchalaht fisheries experts up the northwest coast of Vancouver Island aboard the tribe's lightweight Zodiac. As we returned to the deep canyon fjord of Nootka Sound, a call came over the radio from the First Nation's stewardship boat. Luna was playing at the Gold River dock.
Within minutes, we were looking for the mischievous orca. At first there was no sign of him. We idled slowly from one end of the dock to the other. "False alarm," I thought. Then I saw his head bob up beside the rusty hull of a large boat.
Fisheries coordinator Jamie James leaned over the side of the Zodiac and snapped his fingers below the surface of the water. Luna immediately swam over to us like a happy sea puppy. He seemed to recognize Jamie, and he eyed me with curiosity. I was stunned.
For the next hour, a rambunctious Luna swam back and forth between our boats as we led him from potential trouble and out toward the ocean. He gently pushed us from side to side.
He dove with playful agility beneath the hull and pushed us along from the back of the Zodiac. Luna did backflips and splashed the water with his tail and pectoral fins. He surfed in our wake and rubbed up against the side of the boat.
All I could say — over and over — was, "He's amazing!" I feel blessed to have encountered this special creature. He struck me as a sweet, gentle, childlike spirit.
I took many photographs of Luna that day and have since written about the iconic orca for several publications. It is a compelling narrative.
At a time when salmon runs are at historic lows, northern glaciers are melting at an alarming rate and earthquakes and cyclones are wiping out entire communities, Luna's presence among humans serves as a poignant reminder about our responsibility as stewards over this fragile Earth and its endangered creatures.
Stephan Michaels
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Thursday, 12 June 2008
Next Generation Iphone Launched
The next generation of mobile from Apple - the iPhone 3G - has been revealed to expectant audiences at the World Wide Developers' Conference in San Francisco.
Initial reaction to the product was warm, but many of the technical innovations had been widely expected.
The device's 3G capability had been rumoured, along with a new Global Position System (GPS), allowing users to track their movements.
For buyers it was the price that is likely to prove most attractive.
While the first generation of iPhones were priced at $599 (£300), falling to $399 (£200), the basic (eight gigabyte) version of the new model will go on sale for just $199 (£100).
A 16 gig model will be available to American consumers when the new device goes on sale on July 11th, priced $299 (£150).
Apple chief executive Steve Jobs admitted price was the number one reason the previous incarnation of the product had perhaps failed to meet expectations.
With this in mind, Apple has significantly lowered the price in an attempt to expand market share.
However, the phone will remain exclusive to the 02 network when it is released in the UK – causing some buyers to complain of the negative price connotations of the monopoly.
Apple also announced improvements in download speeds and other technical abilities.
Mr Jobs confirmed there are to be 300 hours of standby time, five hours of 3G talk time, five to six hours of browsing, seven hours of video and 24 hours of audio power.
The new device is expected to be launched in Europe in November.
10/06/2008 11:39:28
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Friday, 6 June 2008
Harrison Ford - Indiana Jones Makes 45m In Midnight Screenings
The new Indiana Jones film, the Kingdom of the Crystal Skull, has reportedly made $4.5 million (£2.27 million) at the US box office after midnight screenings on Wednesday night.
Variety magazine claimed that the fourth Indiana Jones film also made $2.2 million (£1.1 million) in France, Belgium and Switzerland.
Reviews of the eagerly awaited film have been mixed with some critics hailing the return of the famous archaeologist, 19 years after he last appeared on the big screen, as a triumph. Others have been less that flattering regarding Harrison Ford's age and the film's script.
The film received its international premier earlier this week at the Cannes festival.
At the famous film event Ford dismissed criticism of the film claiming that he made the picture for the paying public not the critics.
Indiana Jones, created by George Lucas and Steven Spielberg, first appeared on cinema screens in 1981 in the film Raiders of the Lost Ark.
The franchise included two other movies including Temple of Doom in 1984 and the Last Crusade in 1989.
23/05/2008 12:15:17
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Thursday, 29 May 2008
Gallagher & Appleton tie the knot
Oasis frontman Liam Gallagher has married his long-term partner, singer Nicole Appleton.
According to reports, the couple tied the knot in a low-key civil ceremony in London on Valentine's Day.
The wedding reception reportedly took place at the five-star Landmark Hotel in London.
Appleton has previously spoken about marrying Gallagher, saying: "Marriage is important to me and I love the idea of being married."
The couple, who have been together for nearly eight years, have a seven-year-old son together.
According to reports, the couple tied the knot in a low-key civil ceremony in London on Valentine's Day.
The wedding reception reportedly took place at the five-star Landmark Hotel in London.
Appleton has previously spoken about marrying Gallagher, saying: "Marriage is important to me and I love the idea of being married."
The couple, who have been together for nearly eight years, have a seven-year-old son together.
Wednesday, 28 May 2008
Concord Down
Artist: Concord Down
Genre(s):
Drum & Bass
Discography:
Man for All Seasons METH71 VLS
Year: 2006
Tracks: 2
Kate Hudson now dating Lance Armstrong?
Travolta defends his friend Cruise
Actor John Travolta has spoken up for his friend Tom Cruise, after criticisms of the star following the leaking of a Scientology video on the Internet.
According to People magazine, Travolta said: "[Tom] has - we all have - the right to practice how we feel. It finally becomes unfair."
Travolta claimed that the media invasion into Cruise's life had gone too far.
The former 'Grease' star made the comments at the weekend, while attending the G'Day USA Gala to honour singer Kylie Minogue.
Check out all the photographs from the G'Day USA Gala here.
According to People magazine, Travolta said: "[Tom] has - we all have - the right to practice how we feel. It finally becomes unfair."
Travolta claimed that the media invasion into Cruise's life had gone too far.
The former 'Grease' star made the comments at the weekend, while attending the G'Day USA Gala to honour singer Kylie Minogue.
Check out all the photographs from the G'Day USA Gala here.
Bon Jovi - Sambora Offers Beckham Guitar Lessons
BON JOVI star RICHIE SAMBORA has offered English soccer ace DAVID BECKHAM free guitar lessons.
The guitarist is a big fan of the L.A. Galaxy star and has urged him to give call him if he ever feels like learning the instrument.
He says, "Beckham is a good guy. He's done so much for soccer in the U.S.
"He's such a big name and brought soccer to a different level and its now played in schools. It's just a pity that he doesn't get to play more as he's been injured.
"David should come and see me. I'd gladly give him lessons. I'd be privileged."
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Michael Ellis
Artist: Michael Ellis
Genre(s):
Other
Discography:
I Would Have Given So Much More
Year: 2006
Tracks: 16
Sepia (CD2)
Year: 2005
Tracks: 2
Sepia (CD1)
Year: 2005
Tracks: 8
Perfect Sense (CD1)
Year: 2003
Tracks: 11
Perfect Sense (Bonus CD)
Year: 2003
Tracks: 3
Barry Brown
Britney loses access to boys
Britney Spears' access to her two baby boys has been withdrawn.
A Los Angeles Superior Court judge ordered Spears' children to be placed in the sole care of her ex-husband Kevin Federline, suspending the pop star's visitation rights until "further order of the court."
A hearing has been set for 14 January which will determine how their bitter custody battle is to proceed.
The court ruling came after a dramatic 24 hours for Spears, who has rarely been out of the tabloid headlines over the past year following a string of bizarre incidents.
Last Thursday she was wheeled out of her Los Angeles mansion on a stretcher and taken to the Cedars Sinai hospital for evaluation following a three-hour custody standoff.
Spears had reportedly refused to release her children Sean Preston, two, and Jayden James, one, to Federline's bodyguard.
Video footage of the aftermath of the incident showed Spears alternately smiling and looking distraught as she was lifted into an ambulance.
Los Angeles Police Department spokesman Jason Lee said Spears was being detained and evaluated in hospital because officers had found her under the influence of an unknown substance.
Federline's lawyer Mark Vincent Kaplan said he took no satisfaction for the court ruling in his client's favour.
"I am not happy about anything that has happened recently," he told reporters. "There are no winners right now."
A Los Angeles Superior Court judge ordered Spears' children to be placed in the sole care of her ex-husband Kevin Federline, suspending the pop star's visitation rights until "further order of the court."
A hearing has been set for 14 January which will determine how their bitter custody battle is to proceed.
The court ruling came after a dramatic 24 hours for Spears, who has rarely been out of the tabloid headlines over the past year following a string of bizarre incidents.
Last Thursday she was wheeled out of her Los Angeles mansion on a stretcher and taken to the Cedars Sinai hospital for evaluation following a three-hour custody standoff.
Spears had reportedly refused to release her children Sean Preston, two, and Jayden James, one, to Federline's bodyguard.
Video footage of the aftermath of the incident showed Spears alternately smiling and looking distraught as she was lifted into an ambulance.
Los Angeles Police Department spokesman Jason Lee said Spears was being detained and evaluated in hospital because officers had found her under the influence of an unknown substance.
Federline's lawyer Mark Vincent Kaplan said he took no satisfaction for the court ruling in his client's favour.
"I am not happy about anything that has happened recently," he told reporters. "There are no winners right now."
Nicole Kidman - Kidman Forgot To Vote For Urban
NICOLE KIDMAN forgot to vote for her husband at Sunday's (18May08) Academy of Country Music Awards.
For the first time, fans had the chance to vote for Entertainer of The Year as part of an online vote, but actress Kidman confessed she still hadn't voted for her man as the pair posed for pictures on the red carpet at the Las Vegas prizegiving.
She told reporters, "I didn't get a chance to vote for Keith. I'll do it from my cell phone inside. It's not too late, is it?"
But it appears her vote, if she managed to phone it in, didn't count - Urban was soundly beaten by Kenny Chesney.
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Yoko Ono supports Heather Mills
Speaking on a visit to the dead Beatle’s childhood home in Liverpool, Yoko, 75, said she thought Mills, dubbed Mucca by British tabloids due to her porn past, must have “suffered”.
She added: “It’s not very easy for a woman to be associated with The Beatles. I think all the wives did suffer, but suffer quietly and endured.”
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