Friday, September 14, 2012

BlackBerry Updates Facebook App to Support Birthday, Event Alerts

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Scientists Discover How an Out-of-Tune Protein Leads to Muscle Demise in Heart Failure

ScienceDaily (Sep. 12, 2012) ? A new Johns Hopkins study has unraveled the changes in a key cardiac protein that can lead to heart muscle malfunction and precipitate heart failure.

Troponin I, found exclusively in heart muscle, is already used as the gold-standard marker in blood tests to diagnose heart attacks, but the new findings reveal why and how the same protein is also altered in heart failure. Scientists have known for a while that several heart proteins -- troponin I is one of them -- get "out of tune" in patients with heart failure, but up until now, the precise origin of the "bad notes" remained unclear.

The discovery, published online ahead of print on Sept. 12 in the journal Circulation, can pave the way to new -- and badly needed -- diagnostic tools and therapies for heart failure, a condition marked by heart muscle enlargement and inefficient pumping, and believed to affect more than 6 million adults in the United States, the researchers say.

Troponin I acts as an on-off switch in regulating heart relaxation and contraction and, in response to, adrenaline -- the "flight-fight" response. But when altered, troponin I can start acting as a dimmer switch instead, one that ever so subtly modulates cardiac muscle function and reduces the heart's ability to pump efficiently and fill with blood, the researchers found.

The Hopkins team used a novel method to pinpoint the exact sites, or epicenters, along the protein's molecule where disease-triggering changes occur. They found 14 such sites, six of them previously unknown. In revealing new details about the molecular sequence of events leading up to heart failure, the researchers said their work may spark the development of tests that better predict disease risk and monitor progression once the heart begins to fail.

"Our findings pinpoint the exact sites on troponin I's molecule where disease-causing activity occurs, and in doing so they give us new targets for treatment," says researcher Jennifer Van Eyk, Ph.D., director of the Johns Hopkins Proteomics Innovation Center in Heart Failure.

In the current study, the team analyzed tissue from the hearts of patients with end-stage heart failure and from deceased healthy heart donors. The 14 sites the researchers identified are sites where troponin I binds with phosphate, a process known as phosphorylation.

Phosphate can activate or deactivate many enzymes, thus altering the function of a protein and, in the case of heart failure, ignite disease. The six newly identified sites represent new "hot spots" involved in heart contraction, the researchers say, and could be used as diagnostic markers or a target for treatment to restore function.

The Hopkins researchers found that in some sections of the molecule, phosphorylation ratcheted up the dimmer switch, while ratcheting it down in other sections, but it invariably led to muscle dysfunction.

"Our goal would be to zero in on these new sites, gauge risk of heart failure and, hopefully, restore heart muscle function," Van Eyk says.

Heart failure is a complex progressive disorder, and while cardiac pacemakers can restore or "resynchronize" heart function in many people, about one-third of patients do not improve even with pacemaker therapy in addition to standard medication treatments.

"This is a devastating disorder for which we desperately need new and less invasive therapies," says senior investigator Anne Murphy, M.D., a cardiologist at Johns Hopkins Children's Center.

In their analysis, the researchers used a novel technique, called multiple-reaction monitoring (MRM), which pinpoints the exact locations along the protein's molecule where faulty signaling occurs and disrupts heart muscle function. MRM is an ultra-sensitive type of mass spectrometry that measures the exact size and chemical composition of protein fragments. Phosphorylated protein fragments have different molecular weights than non-phosphorylated ones. In this way, MRM accurately homes in on sites where phosphate is bound to troponin I to modulate heart muscle function.

The researchers found that patients with heart failure had markedly different levels of phosphorylation in certain protein segments compared with healthy heart muscle.

The advantage of MRM analysis -- one of the first non-antibody based troponin I tests -is that it can measure phosphorylation levels without the need for antibodies, the traditional method currently used to monitor heart muscle function. The researchers believe that MRM can be developed as a clinical diagnostic test, and the Hopkins team is already working to develop a test that would measure phosphorlyation levels of proteins in the blood and would allow physicians to monitor the progression of the disease as well as predict which heart attack patients will progress to heart failure. About one-third of them do so.

"Right now, we don't really know which heart attacks patients will develop heart failure and which ones will maintain normal heart muscle function," Murphy says. "Monitoring specific phosphorylation sites might be one way to help us foresee and forestall this complication on an individual patient basis."

Other Johns Hopkins investigators on the study included Pingbo Zhang, Ph.D., Weihua Ji, M.S., Cristobal G. dos Remedios, D.Sc., Jonathan Kirk, Ph.D., and David Kass, M.D.

This work was supported by the National Heart Lung and Blood Institute's Proteomic Initiative contracts NHLBI-HV-10-05(2) and HHSN268201000032C, P01HL081427, P01HL77189-01, and R01 HL63038; by the Johns Hopkins Clinical Translational Science Award (CTSA); and by American Heart Association Postdoctoral Fellowships 10POST4000001 and 11POST7210031.

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The above story is reprinted from materials provided by Johns Hopkins Medicine.

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


Journal Reference:

  1. P. Zhang, J. A. Kirk, W. Ji, C. G. dos Remedios, D. A. Kass, J. E. Van Eyk, A. M. Murphy. Multiple Reaction Monitoring to Identify Site-Specific Troponin I Phosphorylated Residues in the Failing Human Heart. Circulation, 2012; DOI: 10.1161/CIRCULATIONAHA.112.096388

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/health_medicine/heart_disease/~3/VsbDQn3tsUc/120912161927.htm

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Saturday, September 8, 2012

40% of U.S. Mobile Users Will Click an Unsafe Link This Year

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Sharp mortgages itself to the hilt just to keep going

Sharp mortgages itself to the hilt to raise the funds necessary to keep going

Sharp has mortgaged its offices and factory buildings in order to raise the cash it needs to stay in business, according to Reuters. It's cut a deal with banks for nearly $2 billion in short-term credit secured on its assets -- including the factory that reportedly produces displays for the iPhone. Sharp had pinned its hopes on cash from Hon Hai, but the Chinese giant is apparently delaying the money with the aim of gaining more control over Sharp's business. In response, Sharp has pledged to send president Takashi Okuda to meet Hon Hai's Terry Gou in Taipei -- just as soon as it's scraped together the air-fare.

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Friday, September 7, 2012

Thursday, September 6, 2012

Sandra Fluke slams Romney over contraception at DNC

CHARLOTTE, N.C.--Recent law school graduate Sandra Fluke, who became a heroine on the left this year when she appeared at a Democratic hearing to argue for federal subsidies for contraception, spoke on Wednesday at the Democratic National Convention, where she suggested that Mitt Romney would restrict access to birth control if elected.

Fluke told the crowd that under Romney, the country could become a place "in which access to birth control is controlled by people who will never use it; in which politicians redefine rape so survivors are victimized all over again. ... We know what this America would look like. In a few short months, it's the America we could be."

Some of you may remember that earlier this year, Republicans shut me out of a hearing on contraception. In fact, on that panel, they didn't hear from a single woman, even though they were debating an issue that affects nearly every woman. Because it happened in Congress, people noticed. But it happens all the time. Many women are shut out and silenced. So while I'm honored to be standing at this podium, it easily could have been any one of you. I'm here because I spoke out, and this November, each of us must do the same.

During this campaign, we've heard about the two profoundly different futures that could await women?and how one of those futures looks like an offensive, obsolete relic of our past. Warnings of that future are not distractions. They're not imagined. That future could be real.

In that America, your new president could be a man who stands by when a public figure tries to silence a private citizen with hateful slurs. Who won't stand up to the slurs, or to any of the extreme, bigoted voices in his own party. It would be an America in which you have a new vice president who co-sponsored a bill that would allow pregnant women to die preventable deaths in our emergency rooms. An America in which states humiliate women by forcing us to endure invasive ultrasounds we don't want and our doctors say we don't need. An America in which access to birth control is controlled by people who will never use it; in which politicians redefine rape so survivors are victimized all over again; in which someone decides which domestic violence victims deserve help, and which don't. We know what this America would look like. In a few short months, it's the America we could be. But it's not the America we should be. It's not who we are.

We've also seen another future we could choose. First of all, we'd have the right to choose. It's an America in which no one can charge us more than men for the exact same health insurance; in which no one can deny us affordable access to the cancer screenings that could save our lives; in which we decide when to start our families. An America in which our president, when he hears a young woman has been verbally attacked, thinks of his daughters?not his delegates or donors?and stands with all women. And strangers come together, reach out and lift her up. And then, instead of trying to silence her, you invite me here?and give me a microphone?to amplify our voice. That's the difference.

Over the last six months, I've seen what these two futures look like. And six months from now, we'll all be living in one, or the other. But only one. A country where our president either has our back or turns his back; a country that honors our foremothers by moving us forward, or one that forces our generation to re-fight the battles they already won; a country where we mean it when we talk about personal freedom, or one where that freedom doesn't apply to our bodies and our voices.

We talk often about choice. Well, ladies and gentlemen, it's time to choose.

Source: http://news.yahoo.com/blogs/ticket/sandra-fluke-speaks-primetime-democratic-national-convention-022731441--election.html

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