Mapping of cancer cell fuel pumps paves the way for new drugs

Apr. 28, 2013 ? For the first time, researchers at Karolinska Institutet in Sweden have managed to obtain detailed images of the way in which the transport protein GLUT transports sugars into cells. Since tumours are highly dependent on the transportation of nutrients in order to be able to grow rapidly, the researchers are hoping that the study published in the scientific magazine Nature Structural & Molecular Biology will form the basis for new strategies to fight cancer cells.

In order to be able to fuel their rapid growth, cancer tumours depend on transporter proteins to work at high speed to introduce sugars and other nutrients that are required for the cell's metabolism. One possible treatment strategy would therefore be to block some of the transporters in the cell membrane which operate as fuel pumps, thus starving out and killing the cancer cells.

One important group of membrane transporters is the GLUT family, which introduces glucose and other sugars into the cell. Glucose is one of the most important energy sources for cancer cells and GLUT transporters have been shown to play a key role in tumour growth in many different types of cancer.

In the current study, researchers from Karolinska Institutet have performed a detailed study of the way in which suger transport is executed by the protein XylE, from the Escherichia colibacterium, whose function and structure is very similar to GLUT transporters in humans. For the first time, the researchers have described the way in which the protein's structure changes between two different conformations when it binds and transports a sugar molecule.

"In showing details of the molecular structure of the region that bind the sugar, our study opens up the opportunities to more efficiently develop new substances that may inhibit GLUT transporters," says P?r Nordlund at the Department of Medical Biochemistry and Biophysics, one of the researchers behind the study. "Information on the structure of the transport protein facilitates the development of better drugs in a shorter time. Such GLUT inhibitors could potentially be used to treat cancer in the future."

The study may be of significance not just to cancer research but also in the field of diabetes. GLUT plays a key role in diabetes since insulin works by activating the uptake of glucose from the blood by means of GLUT transporters in the cell membrane.

GLUT and the studied XylE transporter belong to the very large group of metabolite transporters called the Major Facilitator Superfamily (MFS), which is important in many diseases and for the uptake of medicines in cells.

"Many aspects concerning molecular mechanisms for the function of GLUT transporters are probably common to many members of the MFS family, which are involved in a broad spectrum of diseases in addition to cancer and diabetes," says P?r Nordlund.

As well as membrane transporters, which have undergone in-depth analysis in the current study, many different membrane proteins pass through the surface membrane of the cells. Their significance to the cell function and the development of drugs has been noted before, not least through the Nobel Prizes that were awarded to researchers who used mechanistic and structural studies to map the function of two other major membrane protein families, G-protein-coupled receptors and ion channels.

The current study has been financed by grants from the Swedish Research Council, the Swedish Cancer Society, the European Molecular Biology Organization (EMBO) and The Danish Council for Independent Research.

Share this story on Facebook, Twitter, and Google:

Other social bookmarking and sharing tools:

---

Story Source:

The above story is reprinted from materials provided by Karolinska Institutet, via AlphaGalileo.

Note: Materials may be edited for content and length. For further information, please contact the source cited above.

---

Journal Reference:

1. Esben M Quistgaard, Christian L?w, Per Moberg, Lionel Tr?saugues, P?r Nordlund. Structural basis for substrate transport in the GLUT-homology family of monosaccharide transporters. Nature Structural & Molecular Biology, 2013; DOI: 10.1038/nsmb.2569

Note: If no author is given, the source is cited instead.

Disclaimer: This article is not intended to provide medical advice, diagnosis or treatment. Views expressed here do not necessarily reflect those of ScienceDaily or its staff.

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/~3/YpfcBJy_z0w/130428144853.htm

e cards kate upton sports illustrated outback chaka khan taylor swift safe and sound delilah nevis

Justin Bieber and Selena Gomez: Cuddling, Shirtless, SEXY in New Photo!

Source:

soda bread recipe vanderbilt evan mathis staff sgt. robert bales jason russell norfolk state st patrick s day parade

Early Earth's chlorine blown away by giant impacts

Element has long puzzled scientists because modern levels are so low

By Erin Wayman

Web edition: April 24, 2013

Earthlings may owe a debt of gratitude to the enormous miniplanets that smashed into the planet in its youth. Such collisions might have knocked away much of the supply of chlorine concentrated on the planet?s surface, geochemists propose. Had that loss not occurred, the world?s oceans would have been too salty for complex life to thrive, they suggest.

The scenario may explain why Mars, which suffered fewer large impacts, may have more than twice as much chlorine as Earth does, the researchers report April 16 in Earth and Planetary Science Letters.

?The story seems to hang together pretty well,? says James Brenan, a geologist at the University of Toronto who wasn?t involved in the study. ?Life, probably over a fairly long time, might have been able to adapt to this environment, though certainly things would be different than today.?

One snag is that the idea is ?a very difficult thing to test,? says geochemist Ray Burgess of the University of Manchester in England.

The composition of ancient meteorites, which are remnants of the raw material that built the planets, indicates that Earth should have 10 times as much chlorine as it does. The missing chlorine has perplexed scientists for decades. In 1995, geochemist William McDonough suggested that chlorine was dragged to Earth?s center by iron, nickel and other metals that formed the planet?s core.

Normally, chlorine and other elements known as halogens don?t readily dissolve in metals or often combine with other elements to form minerals found in rocks. But perhaps under the intense heat and pressure of the core, chlorine might have become more willing to mix with metal. ?I wasn?t happy with putting it in the core,? says McDonough, of the University of Maryland in College Park. But he didn?t know what else to do with it. ?I was scratching my head,? he says.

The new work suggests that, in fact, the core is not where chlorine went. In lab tests, Zachary Sharp of the University of New Mexico in Albuquerque and David Draper of the NASA Johnson Space Center in Houston approximated the conditions of the core and observed chlorine?s behavior. They added iron metal, rocks typical of the mantle and a chlorine compound to a capsule heated to 1900? Celsius under pressures about 80,000 times higher than Earth?s atmospheric pressure. The result: Chlorine still didn?t dissolve in iron. That means chlorine probably isn?t hiding out in the core, Sharp says.

So he and Draper looked elsewhere for a solution. After ruling out the possibility that Earth never accumulated chlorine in the first place, the pair concluded that the incipient Earth rammed into giant planetary bodies more than 4 billion years ago and the repeated impacts blew the element away.

The explanation hinges on the peculiarity of chlorine. Unlike elements that mostly end up in rocks and metals, most of Earth?s chlorine is in salt deposits and brines or dissolved in the ocean. Because the element is concentrated on the surface, giant impacts in the past would have stripped away a good chunk of Earth?s chlorine supply, Sharp and Draper say.

Had the early impacts not happened, Sharp says, ?the Earth would have been a halogen-poisoned planet.? The oceans would be as salty as the Dead Sea, and high salinity would reduce precipitation. With less rain, there would be less erosion on land and fewer nutrients washing into the sea. In such a world, he says, ?it would be much more difficult for [complex] life to evolve.?

McDonough acknowledges that the new work disproves the idea that chlorine is trapped in the core. However, he?s not yet convinced that cosmic crashes removed the element. Even with the massive collision that created the moon, the pull of gravity returned to Earth most of the material that had been kicked into space, he says. ?But I don?t have a better idea.?

To strengthen the argument, planetary geochemist Mikhail Zolotov of Arizona State University in Tempe suggests that the team develop simulations to assess how impacts could have affected elements in the young Earth?s atmosphere, oceans and crust. The team could also investigate whether other elements preferentially found on the surface are also lower than expected. ?

Source: http://www.sciencenews.org/view/generic/id/349930/title/Early_Earths_chlorine_blown_away_by_giant_impacts

kendall marshall whitney houston news sylvia plath whitney houston autopsy results obama trayvon jim yong kim michael bush

Tech company wants to launch ?space harpoon? to clean up debris

(Releads, adds Sheikh Mohammed's comments, Dubai dateline) DUBAI/LONDON, April 24 (Reuters) - Godolphin are to close the Newmarket stable of trainer Mahmood Al Zarooni while dope tests are carried out on all racehorses in his care after 11 tested positive for steroids, Dubai's ruler Sheikh Mohammed bin Rashid al-Maktoum said on Wednesday. "There can be no excuse for any deliberate violation," Sheikh Mohammed, also Prime Minister of the United Arab Emirates, said in a statement sent to Reuters. ...

Source: http://news.yahoo.com/blogs/sideshow/tech-company-wants-launch-space-harpoon-clean-debris-165233213.html

Rob Parker Comcast Pokemon X and Y Rob Ryan bethenny frankel sacramento kings alex jones

High score: Man busted with pot-stuffed Pac-Man arcade game

Yannick LeJacq , NBC News contributor ? ? ? 3 hrs.

Video games and marijuana may have a rich shared history, but the two came together in an unexpected combination last week in Orangeburg, S.C., when local and federal authorities apprehended a man for smuggling 55 pounds of marijuana that had been stashed inside an arcade cabinet. A Pac-Man arcade, no less.

Authorities first arrested Luis Tyler on April 16 following an undercover investigation, Keisa Gunby, director of media relations for Orangeburg County Sheriff's Office, told NBC News.

"We knew that he was going to be receiving this video game and it was going to have narcotics in it, so we did a traffic stop before he was able to get where he was going with it," Gunby said.

Gunby said she couldn't remember another case involving such a machine, and told us that the Pac-Man cabinet was so tightly packed with pot, it was inoperable as a game console.

"It can't be a functional machine with that much marijuana inside," Gunby said. "It was never going to operate as intended."

While Tyler was apprehended last Tuesday and South Carolina Judge Derrick Dash subsequently set bond at $75,000 the following day, Sheriff Leroy Ravenell didn't announce the bust until Saturday, April 20. Also known as "4/20," that day is widely observed by North American pot smokers as a holiday.

The timing was a sheer coincidence, said Gunby, attributing the delay to remaining questions concerning Tyler's prosecution.

"We are still considering whether he's going to face federal charges or state charges," Gunby said.

The department did make use of the gaming angle, however.

"Our efforts to make Orangeburg safe will not stop," Ravenell is quoted as saying in a press release. "We ... will continue to investigate the criminals in our community and make arrests. You may be looking for a high score but what you'll get is game over!"

? via Kotaku

Yannick LeJacq is a contributing writer for NBC News who has also covered games for Kill Screen, The Wall Street Journal and The Atlantic. You can follow him on Twitter at @YannickLeJacq and reach him by email at ylejacq@gmail.com.

Source: http://feeds.nbcnews.com/c/35002/f/653377/s/2b1490fe/l/0L0Snbcnews0N0Ctechnology0Cingame0Chigh0Escore0Eman0Ebusted0Epot0Estuffed0Epac0Eman0Earcade0Egame0E6C956630A6/story01.htm

one world trade center bks new dark knight rises trailer khloe and lamar oklahoma city thunder sunoco titanic ii

Antares Rocket Launch Is A Success, In Test Of Orbital Supply Vehicle

The Antares rocket sits ready, moments before launch at NASA's Wallops Flight Facility.

NASA TV

The Antares rocket sits ready, moments before launch at NASA's Wallops Flight Facility.

NASA TV

The Antares rocket launch is back on for 5 p.m. ET Sunday afternoon, as engineers and spectators look for the rocket to lift off from a launch pad at NASA's Wallops Flight Facility. A check of all systems at 10 minutes before its launch was positive.

Update at 5:10 p.m. ET. Orbit Achieved, Payload Separated:

Antares moved smoothly through its stages and achieved orbit, drawing applause from engineers watching in the control room. Soon after, it delivered its practice payload into orbit around the Earth. The test mission has about eight more minutes remaining.

Update at 5:02 p.m. ET. Liftoff Is A Success:

The Antares rocket soared above Wallops Island Sunday afternoon. Just before the engines were throttled down in Stage 1, the vehicle was traveling at more than 7,000 miles per hour. Our original post continues:

The mission had been postponed twice this week, after a connecting cable came loose on Wednesday and unfavorable winds forced a one-day delay on Saturday. Officials believe the launch may be visible from sites all along the eastern U.S. coast.

Around 3:30 p.m. ET Sunday, the rocket was approved for launch and fueling of the vehicle began, NASA reported.

The NASA facility is located just behind the beach on Wallops Island on Virginia's Eastern Shore. Antares is a product of a joint development project between NASA and Orbital Sciences Corp., based in Virginia.

As NPR's Geoff Brumfiel reported Wednesday, a successful test would eventually make Orbital "the second private company after California's SpaceX to dock with the space station."

Source: http://www.npr.org/blogs/thetwo-way/2013/04/21/178289293/antares-rocket-launch-is-a-go-in-test-of-space-station-supply-vehicle?ft=1&f=1007

Red Widow

?Well I didn?t vote for you!? ?You don?t vote for kings!? ?Well how?d you become king, then?? (Unqualified Offerings)

Share With Friends: | | Politics - Top Stories Stories, News Feeds and News via Feedzilla.

Source: http://news.feedzilla.com/en_us/stories/politics/top-stories/300630447?client_source=feed&format=rss

US weekly amelia earhart Sally Ride Ichiro minka kelly James Holmes court Rupert Sanders