DNA damage: The dark side of respiration

Thursday, May 23, 2013

Adventitious changes in cellular DNA can endanger the whole organism, as they may lead to life-threatening illnesses like cancer. Researchers at Ludwig-Maximilians-Universitaet (LMU) in Munich now report how byproducts of respiration cause mispairing of subunits in the double helix.

The DNA in our cells controls the form and function of every cell type in our bodies. The instructions for this are encoded in the linear sequence of the four subunits found in DNA, the bases adenine (A), cytosine (C), guanine (G) and thymine (T). Random changes in the sequence can lead to cell dysfunction, and may result in unrestricted cell proliferation and malignancies. Mutations can be induced by a variety of agents. For example, cellular respiration, i.e. the reduction of inspired oxygen to water, which powers cell function, also generates highly reactive oxygen species that can damage DNA, with the purine bases G and A being particularly susceptible to this kind of attack.

"Reactive oxygen species are responsible for two different sorts of DNA damage, as they induce formation of both 8-oxo-G and FaPy-G," says Professor Thomas Carell of the Department of Chemistry at LMU. In 2004, work done by Carell and his team defined how 8-oxo-G generates mutations. However, the basis for the mutagenic effect of FaPy-G has remained obscure ? until now. In their latest publication, Carell and his colleagues describe how FaPY-G leads to mispairing of bases in the double helix.

Pernicious partner swapping

One G in one strand of the double helix normally matches up with a C on the other, forming a G:C pair. But as a consequence of damage by reactive oxygen species, the guanine base may be transformed into FaPy-G, so that we get a FaPy-G:C base pair. "We have now shown that, in the course of DNA replication prior to cell division, FaPy-G interacts with adenine, leading to the formation of FaPy-G:A base pairs. This partner swap is unusual, since unmodified guanine normally does not team up with adenine," Carell notes.

FaPy-G is subsequently recognized as abnormal and is removed by DNA repair enzymes. The missing base is replaced by a T ? which is the usual partner for A. The net result is that the original G:C base pair has been converted into an A:T pair, and the base sequence has undergone a potentially dangerous mutation.

This outcome is made possible by the fact that the cell's damage-control systems find it surprisingly difficult to distinguish the normal guanine base from its aberrant derivative FaPy-G during DNA replication. "That this defect then leads to mispairing with adenine is one of the main reasons for the spontaneous development of tumors," says Carell. "So with every breath we take, our risk of getting cancer goes up by a teeny-weeny bit." Further insights into the reasons why FaPy-G often eludes the cell's detection and correction systems could help to improve the treatment of cancer, as the inhibition of DNA repair processes in tumor cells increases their sensitivity to chemotherapeutic drugs.

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Article: http://www.nature.com/nchembio/journal/vaop/ncurrent/full/nchembio.1254.html

Ludwig-Maximilians-Universit?t M?nchen: http://www.uni-muenchen.de

Thanks to Ludwig-Maximilians-Universit?t M?nchen for this article.

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Source: http://www.labspaces.net/128372/DNA_damage__The_dark_side_of_respiration

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If MQM workers don't reform themselves, they will lose me: Altaf ...

MQM chief says his family member?s went abroad to save their lives.

MQM chief Altaf Hussain PHOTO: MQM

LONDON:?If my party workers fail to reform themselves, they will lose me as their leader forever, Muttahida Quami Movement (MQM) chief Altaf Hussain said on Friday.

Altaf was speaking to members of the interim Rabita Committee and other party workers.

?I never taught MQM workers to take bribes, be corrupt or put undue pressure on people for favours,? he said.

Addressing the issue of his stay away from home, Altaf told his party members that his family members went abroad to save their lives.

He said his family worked hard while living in a foreign land.

Delving more into his family and political affairs, the MQM chief said he never favoured his family with gains from his political movement.

?I did not give party tickets to my relatives in elections,? he added.

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Source: http://tribune.com.pk/story/553850/never-taught-mqm-workers-to-take-bribes-or-be-corrupt-altaf-hussain/

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Molecule that triggers sensation of itch discovered

May 23, 2013 ? Scientists at the National Institutes of Health report they have discovered in mouse studies that a small molecule released in the spinal cord triggers a process that is later experienced in the brain as the sensation of itch.

The small molecule, called natriuretic polypeptide b (Nppb), streams ahead and selectively plugs into a specific nerve cell in the spinal cord, which sends the signal onward through the central nervous system. When Nppb or its nerve cell was removed, mice stopped scratching at a broad array of itch-inducing substances. The signal wasn't going through.

Because the nervous systems of mice and humans are similar, the scientists say a comparable biocircuit for itch likely is present in people. If correct, this start switch would provide a natural place to look for unique molecules that can be targeted with drugs to turn off the sensation more efficiently in the millions of people with chronic itch conditions, such eczema and psoriasis.

The paper, published online in the journal Science, also helps to solve a lingering scientific issue. "Our work shows that itch, once thought to be a low-level form of pain, is a distinct sensation that is uniquely hardwired into the nervous system with the biochemical equivalent of its own dedicated land line to the brain," said Mark Hoon, Ph.D., the senior author on the paper and a scientist at the National Institute of Dental and Craniofacial Research, part of the National Institutes of Health.

Hoon said his group's findings began with searching for the signaling components on a class of nerve cells, or neurons, that contain a molecule called TRPV1. These neurons, with their long nerve fibers extending into the skin, muscle, and other tissues, help to monitor a range of external conditions, from extreme temperature changes to detecting pain.

Yet little is known about how these neurons recognize the various sensory inputs and, like sorting mail, know how to route them correctly to the appropriate pathway to the brain.

To fill in more of the details, Hoon said his laboratory identified in mice some of the main neurotransmitters that TRPV1 neurons produce. A neurotransmitter is a small molecule that neurons selectively release when stimulated, like a quick pulse of water from a faucet, to communicate sensory signals to other nerve cells.

The scientists screened the various neurotransmitters, including Nppb, to see which ones corresponded with transmitting sensation.

"We tested Nppb for its possible role in various sensations without success," said Santosh Mishra, lead author on the study and a researcher in the Hoon laboratory. "When we exposed the Nppb-deficient mice to several itch-inducing substances, it was amazing to watch. Nothing happened. The mice wouldn't scratch."

Further experiments established that Nppb was essential to initiate the sensation of itch, known clinically as pruritus. Equally significant, the molecule was necessary to respond to a broad spectrum of pruritic substances. Previous research had suggested that a common start switch for itch would be unlikely, given the myriad proteins and cell types that seemed to be involved in processing the sensation.

Hoon and Mishra turned to the dorsal horn, a junction point in the spine where sensory signals from the body's periphery are routed onward to the brain. Within this nexus of nerve connections, they looked for cells that expressed the receptor to receive the incoming Nppb molecules.

"The receptors were exactly in the right place in the dorsal horn," said Hoon, the receptor being the long-recognized protein Npra. "We went further and removed the Npra neurons from the spinal cord. We wanted to see if their removal would short-circuit the itch, and it did."

Hoon said this experiment added another key piece of information. Removing the receptor neurons had no impact on other sensory sensations, such as temperature, pain, and touch. This told them that the connection forms a dedicated biocircuit to the brain that conveys the sensation of itch.

But the scientists had stepped into a conundrum. Previous reports had suggested that another neurotransmitter called GRP might initiate itch. If that wasn't the case, where did GRP fit into the process?

They tested the receptor neurons that express GRP, finding the previous reports were correct about this molecule relaying the signal to the central nervous system. GRP just enters the picture after Nppb already has set the sensation in motion.

Based on these findings, Nppb would seem to be an obvious first target to control itch. But that's not necessarily the case. Nppb also is used in the heart, kidneys, and other parts of the body, so attempts to control the neurotransmitter in the spine has the potential to cause unwanted side effects.

"The larger scientific point remains," said Hoon. "We have defined in the mouse the primary itch-initiating neurons and figured out the first three steps in the pruritic pathway. Now the challenge is to find similar biocircuitry in people, evaluate what's there, and identify unique molecules that can be targeted to turn off chronic itch without causing unwanted side effects. So, this is a start, not a finish."

Source: http://feeds.sciencedaily.com/~r/sciencedaily/top_news/top_health/~3/x_3jku_kk-s/130523143348.htm

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Loom Is Building A Better iCloud

Barely a month or two after launching the Y Combinator-backed?photo-sharing service Popset, the team realized they were solving the wrong problem. Users weren’t struggling to share their photos with groups; they needed tools to help them organize and manage their photo libraries across a variety of platforms and services. So the company decided to change its course, and today it’s announcing what it has in store: Loom, a cloud storage and syncing service that’s like a better alternative to iCloud. “People were requesting features and giving us feedback that caught our attention,” explains Popset and now Loom co-founder Jan Senderek. After interviewing hundreds of users over a month’s time, the founders had a better idea of what its user base wanted. People told the team of their awful routines for managing photos – backing them from iPhones to external hard drives, having to sync them through iTunes, how quickly the photos ate up precious disk space on their portable devices and MacBook SSD drives, and so on. “There are so many thing that are wrong, and it’s kind of obvious how to solve that – by simply putting everything in the cloud and making it accessible to you on all your devices,” says Senderek. That, of course, is the promise of Apple’s iCloud. But it doesn’t seem to work as well as it should. In recent months,?Apple users and developers have become?increasingly frustrated with iCloud, which has proved to be difficult, buggy, and confusing to end users. “People don’t really understand iCloud. They don’t understand what Photostream is or how it works,” Senderek explains. “It actually makes the problem worse.” Photostream,?which saves the last 1,000 photos?on your device, appears like a separate album, which also confuses some users. The team, which also includes co-founders Philipp Wein?and?Daniel Wagner, realized they had a choice to make. They could either double-down on Popset or respond to the problems users wanted fixed with a whole new product. They chose the latter. Popset users were notified at the beginning of this month that the service would be closing in June, and were offered a downloadable .zip file of the photos they had shared. The new product, Loom, puts all your photos and videos in the cloud, allowing you to empty your Camera Roll and reclaim lost disk space. Designed to replace the native Photos app, Loom instead uses smart technology to intelligently cache photos and

Source: http://feedproxy.google.com/~r/Techcrunch/~3/s32lehF42JI/

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Japan's PM Abe defends policies as markets settle

TOKYO (AP) ? Japan's top leaders are defending the economic strategies championed by Prime Minister Shinzo Abe, though the central bank chief acknowledged a need for better communication with financial markets, a day after Tokyo shares suffered their worst loss since the 2011 tsunami disaster.

Bank of Japan Gov. Haruhiko Kuroda acknowledged Friday the need for careful handling of aggressive monetary policies aimed at breaking the world's third-largest economy free of deflation, or falling prices, that has hobbled growth by slowing investment and consumer spending.

"We are undertaking very flexible market operations and interest rate volatility should be curbed as much as possible," Kuroda told a regional conference in Tokyo, a day after 10-year government bond yields breached 1 percent for the first time in a year. By Friday afternoon they were at about 0.83 percent, near their recent trading level.

"Communication and dialogue with the markets should be strengthened," Kuroda said. "The markets should be stabilized through various channels as we work on the wider economy to establish a favorable growth cycle, and prices should rise gradually."

Kuroda, Abe and other officials said they will stick to the "Abenomics" program of extreme monetary stimulus, government spending and reforms aimed at reviving growth after two decades of stagnation.

The central bank is buying some 70 percent of all new Japanese government bonds as it pumps money into the economy, aiming to double the volume of cash in circulation and bank reserves and push prices higher. Kuroda launched the program in early April, saying he expected it would help keep long-term bond yields low. But as investors have shifted their portfolios out of bonds and into the booming share market, yields have actually risen, adding to worries over the eventual costs Japan will face in managing its huge public debt.

On Thursday, dismal manufacturing data from China coupled with the concerns about Abenomics triggered a sell-off in Tokyo, where the Nikkei 225 fell 7.3 percent, as investors cashed in on recent gains. Shares rebounded early Friday but by mid-afternoon were down another 2 percent.

Abe told a parliamentary session Friday that the government was keeping a close eye on the markets. But he said Japan would "firmly proceed with measures to ensure sustainable government finances and secure market confidence."

The aim is to bring about long-term improvements, said Finance Minister Taro Aso.

"Japan's credibility will increase if it can end prolonged deflation" through Abe's policies, he told reporters.

Source: http://news.yahoo.com/japans-pm-abe-defends-policies-markets-settle-042216768.html

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hi my t mobile uk carrier no longer shows enable LTE Toggel just 3G Toggle in the mobile data section after messing about with the file inside the folder. is their a way to get the LTE toggle back whit out restoring my phone and not losing my jailbreak.

Source: http://www.jailbreakqa.com/questions/182339/how-to-restorefix-iphone-5-carrier-bundes

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The new consoles from Microsoft, Nintendo and Sony

An audience member photographs the stage at the unveiling of Microsoft Corp.'s next-generation Xbox One entertainment and gaming console system, Tuesday, May 21, 2013, in Redmond, Wash. (AP Photo/Ted S. Warren)

An audience member photographs the stage at the unveiling of Microsoft Corp.'s next-generation Xbox One entertainment and gaming console system, Tuesday, May 21, 2013, in Redmond, Wash. (AP Photo/Ted S. Warren)

Marc Whitten, Microsoft Corp.'s chief production officer of interactive entertainment, talks about the features of the next-generation Xbox One entertainment and gaming console system, Tuesday, May 21, 2013, at an event in Redmond, Wash. (AP Photo/Ted S. Warren)

Photographers crowd around Microsoft Corp.'s next-generation Xbox One entertainment and gaming console system after it was officially revealed, Tuesday, May 21, 2013, at an event in Redmond, Wash. It's been eight years since the launch of the Xbox 360. The original Xbox debuted in 2001, and its high-definition successor premiered in 2005. (AP Photo/Ted S. Warren)

This product image released by Microsoft shows the new Xbox One entertainment console that will go on sale later this year. Microsoft is seeking to stay ahead of rivals in announcing that new content that can be downloaded for the popular "Call of Duty" game will launch first on Xbox One. Microsoft says more games will be shown at next month's E3 video game conference in Los Angeles. (AP Photo/Microsoft)

Microsoft Corp.'s Xbox One entertainment and gaming console system is put display for media after its unveiling Tuesday, May 21, 2013, at an event in Redmond, Wash. The Xbox One, a next-generation entertainment console that promises to be the one system households will need for games, television, movies and other entertainment, will go on sale later this year. (AP Photo/Ted S. Warren)

NEW YORK (AP) ? Microsoft is the last of the three big video game console makers to unveil its latest gaming system. The unveiling comes nearly eight years after the Xbox 360 went on sale. It follows last fall's debut of Nintendo's Wii U and a preview in February of the upcoming PlayStation 4 from Sony.

Each machine has a set of features designed to draw gamers away from rival consoles. There's one thing all three have in common, though: They are about more than gaming and include entertainment services such as television, movies and music.

Here's a closer look at the three systems. More details are expected at the E3 video game conference in Los Angeles next month.

? Wii U (Nintendo)

The Japanese gaming company launched the Wii U, the follow-up to its popular Wii, in November, making it the only new console out for last year's holiday season. The console features a tablet-like controller with a touch screen, called the GamePad, which can be used to control games on the TV set or to play games separately, as you would on a regular tablet computer. It also allows someone with a GamePad to have a different experience with a game than someone playing it at the same time with a regular Wii controller.

The GamePad also serves as a fancy remote controller to navigate a TV-watching feature called TVii. The service groups your favorite shows and sports teams together, whether it's on live TV or an Internet video service such as Hulu Plus. And it offers water-cooler moments you can chat about on social media.

Unlike the Wii, the Wii U features high-definition graphics. In doing so, Nintendo's system catches up to the years-old Xbox 360 from Microsoft and the PlayStation 3 from Sony.

Sales of the Wii U have been disappointing, with 3.5 million sold as of March 31, the end of Nintendo's fiscal year. Nintendo Co. had originally expected to sell 5.5 million units and later lowered the forecast to 4 million, but it still fell short.

Price: Starts at $300 but some retailers have offered it at lower prices.

? PlayStation 4 (Sony)

Sony shared some details about the PlayStation 4 in February, but it didn't show what the console would look like. The company said the PS4 would essentially be a "supercharged PC," much like the Xbox. That's a big departure from the old and idiosyncratic PlayStation design and should make it easier for developers to create games.

But the adoption of PC chips also means that the new console won't be able to play games created for any of the three previous PlayStations. Players will have to stream older games over the Internet.

Other new features revolve around social networking and remote access. With one button, you can broadcast video of your game play so friends elsewhere can watch. You can also run a game on the PS4 to stream over the Internet to Sony's mobile gaming device, the PlayStation Vita, which debuted last year.

The PlayStation online network will have access to Sony's video and music services, as well as Netflix, Hulu and Amazon ? as long as you have subscriptions to those services. You'll also be able to access Facebook.

The PS4 will have a Blu-ray disc drive for movies, just like the PS3. The console will go on sale this holiday season, though Sony Corp. has not disclosed an exact date.

Price: Not yet announced.

? Xbox One (Microsoft)

Microsoft's new console seeks to deliver the Holy Grail of home entertainment ? an all-in-one device that lets you watch television, play movies, listen to music and browse the Internet as well as play video games.

The Xbox One lets you use voice commands to switch between watching TV and playing "Call of Duty," or ask "What's on HBO?" to view a TV channel guide. Simply connect your cable or satellite set-top box to the game machine with an HDMI cable.

A new version of Microsoft's camera-based Kinect controller offers better motion and voice detection than the one currently available. Unlike the Xbox 360, the Xbox One will require Kinect, which will come with the package.

Microsoft also reached a multiyear deal with the National Football League to develop new interactive viewing experiences, such as the ability to watch games, chat with other fans, view statistics, access highlights in real time and gather fantasy information about players and teams ? all on a single screen.

Although Nintendo's Wii was the most popular of the three at first, the Xbox 360 has outsold its rivals in recent years largely because of its robust online service, Xbox Live, which allows people to play games with others online for as much as $60 a year with annual plans. Activision's "Call of Duty," has been a driving force behind Xbox Live, and Microsoft said players will be able to download new content for upcoming titles in the series on the Xbox One before any other system.

The new console will also add the ability to play Blu-ray discs, matching what Sony has in its older PlayStation 3. What it won't play are games for the Xbox 360.

Microsoft said the system will launch this year, but it did not give a date during Tuesday's unveiling.

Price: Not yet announced.

Associated Press

Source: http://hosted2.ap.org/apdefault/495d344a0d10421e9baa8ee77029cfbd/Article_2013-05-21-Games-Xbox-Big%20Three%20Consoles/id-f0f7165741dd474d9166f6d6e637ac38

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