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June 20, 2013
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  1. article What's Up UA? - $6M Grant Boosts Molecular Heart Research

    Wednesday, June 19, 2013 1:00 pm

    A $6 million grant from Fondation Leducq, a French non-profit health research foundation fostering international efforts to combat cardiovascular disease, will boost an interdisciplinary, collaborative push to better understand how the heart deals with mechanical stress under healthy conditions and in the case of a defect. 
     
    Henk Granzier, a professor in the department of physiology and the Molecular Cardiovascular Research Program at the University of ArizonaCollege of Medicine, is one of two principal investigators leading the project, which was awarded as a transatlantic network grant, connecting scientists from seven institutions in Europe and the U.S. 
     
    "Many networks compete for this grant, and it is a great honor to be one of the very few that were selected for funding," said Granzier, who will oversee all projects, coordinate and communicate with the network collaborators and assist designing experiments, analyzing data and publishing scientific results. 
     
    The research endeavor revolves around titin, a protein that acts as a "molecular spring" and plays important roles in how muscle cells register mechanical stress (see UANews story, "UA Researcher Studies Protein's Link to Heart Disease"). Titin has moved into the spotlight of cardiovascular research once it was found that mutations in the titin gene are involved in many heart defects.
     
    "With this project, we want to try and understand the interplay between mechanical stress and heart disease, and how titin factors into all of that," said Granzier, who is also a member of the UA BIO5 Institute and holds the Allan and Alfie Norville Endowed Chair for Heart Disease in Women Research at the UA's Sarver Heart Center. 
     
    "You have billions of titin molecules in your heart, where they help it contract and expand," he said. "Titin is very important to make sure your heart doesn't expand too much or too little, so it doesn't overfill or under-fill with blood."
     
    But the molecule, which occurs not only in heart muscle but skeletal muscle as well, does much more than that. 
     
    "Titin acts as a sensor enabling a heart muscle cell to measure mechanical stress," Granzier explained. "When you lift weights, titin senses the added load and interacts with proteins that trigger signaling cascades, which in turn activate genes to crank out more muscle material, so your muscles become bulkier."
     
    Scientists hope that once they better understand the processes at a molecular level, they can develop therapies for conditions that are untreatable now. 
     
    "A big goal of this grant is to understand how mutations in titin cause pathological changes," Granzier said. "We'll focus largely on titin and all the proteins that interact with it. So far, we know of more than 20."
     
    For example, one particular mutation in the titin gene is known to cause a disease called ARVC, or arrhythmogenic right ventricular cardiomyopathy, an inherited heart muscle disorder where damaged heart muscle is gradually replaced by non-muscle tissue. 
     
    "This particular mutation makes titin more susceptible to breaking down," Granzier said. "Others truncate the protein so it loses pieces of its functionality."
     
    BIO5's Genetically Engineered Mouse Models (GEMM) Core, directed by Tom Doetschman, developed a mouse model allowing Granzier to study the mechanisms that underlie this disease. 
     
    "We genetically engineered this mutation to replicate the human disease in the mouse heart, and then we study the mouse to tease apart the disease mechanism under controlled conditions," Granzier said.
     
    A different series of genetic alterations in titin's DNA sequence was found to be the causal defect in about one third of individuals afflicted with a condition called dilated cardiomyopathy – another form of heart failure. Affected individuals frequently develop severe heart failure in their 30s or 40s.
     
    "We want to study this in this grant as well," said Granzier. "How do the mutations lead to the diseased heart?"
     
    To find answers, Granzier and his colleagues apply mouse genetics to eliminate certain titin-binding proteins and see how that changes the sensing and the enlargement of the heart.
     
    "What we want to know is, 'If you have a certain titin binding partner missing, how does the system respond and possibly cause diseases?'" Granzier said, adding that the six diseases that have so far been linked to titin are likely only the tip of an iceberg.
     
    "As more and more high-throughput sequencing technologies become available, my guess is we will find many more diseases that involve titin," he added. "And as awareness of these defects increases, it will become possible to screen family members for such mutations."
     
    Granzier's lab has established a worldwide reputation in titin research by studying the protein and its interactions at every scale, from the individual molecule to the entire heart.
     
    Using an atomic force microscope, the group can make measurements on single titin molecules.
     
    "We can measure characteristics like strength and elasticity of the molecule, and how those are affected by mutations in the titin gene," Ganzier explained. "We also study the mechanics of single cells isolated from the heart. And we can genetically alter the titin gene, take out pieces or add pieces to it, to mimic the mutations that we know exist in patients."
     
    Through these studies, the group discovered that the mutations that causes ARVC weakens the molecule, causing the "spring structure" to unfold. 
     
    "Normally the molecule folds into domains," Granzier said. "It resembles a string of pearls, and when you stretch the molecule, the pearls line up and you pull them taut. But if you have a mutation, it weakens the structure of the domains. The pearls unravel and once the molecule starts breaking down, the mechanical sensing ability is destroyed and the elasticity is messed up."
     
    Although therapies might not become available for a while, knowing what causes the trouble is a critically important first step, Granzier pointed out.
     
    Some day, therapeutics could be developed that interact with the weak spot in the mutated titin molecule and make it stronger. Another approach, currently tested for muscular dystrophy, involves drugs homing in on the machinery inside the cell that manufactures the protein from its genetic blueprint, instructing it to skip the mutated parts. 
     
    "Once we understand the sensing mechanisms of titin and how they are affected by mutations, we could ultimately come up with drugs that lessen the impact of the disease or prevent it altogether," Granzier said.
     
    Under the network grant, the collaboration will exchange expertise, reagents, genetically modified mouse models and researchers to maximize collaboration and results and tackle all aspects of these diseases. 
     
    "It is a huge honor for Henk and the UA to lead this international, multidisiplinary project from Fondation Leducq to decipher the impact of mutations in contractile proteins on human cardiac myopathies," said Carol Gregorio, who heads the Molecular Cardiovascular Research Program and is a collaborator on the grant. 
     
    In addition to the UA, the main research centers participating on the grant are the University of Heidelberg, Germany; University of California San Diego School of Medicine; National Heart & Lung Institute at the Imperial College London; the University of Liverpool; French biotech company Genethon; and the University of Pennsylvania School of Medicine. 
     

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  2. article Police Reports -- Week of June 16

    Wednesday, June 19, 2013 4:00 am

    Marana

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  3. article Summit Hut expands into the Northwest

    Wednesday, June 19, 2013 4:00 am

    Originally opened by two teenagers back in 1967, Summit Hut has kept its customers happy by providing quality outdoor products and services. The store is expanding into the Northwest area on North Oracle Road.

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  4. article Making summer fun to teach your kids life lessons

    Monday, June 17, 2013 5:00 pm

    (BPT) - Ah, the hot days of summer when a neighborhood lemonade stand is the perfect place to buy – or sell – a cold, refreshing drink. While a lemonade stand is a classic summer activity for kids and their parents, it’s also a great way to help teach children about earning money, building community and expressing creativity.

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  5. article Tips On Trucking For DIY Movers

    Thursday, June 13, 2013 4:44 am

    (NAPSI)—When it’s time to move to your college dorm, your first apartment, your family house, your scaled-down empty nest or whenever you have a new home, you may be able to save time, trouble and money by doing it yourself.

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  6. youtube This is the End -- Red Band Trailer

    Wednesday, June 12, 2013 8:43 am

    The comedy This Is The End follows six friends trapped in a house after a series of strange and catastrophic events devastate Los Angeles. As the world unravels outside, dwindling supplies and cabin fever threaten to tear apart the friendships inside. Eventually, they are forced to leave the house, facing their fate and the true meaning of friendship and redemption.Director: Seth Rogen/Evan GoldbergRelease: 6/12/2013Studio: Columbia PicturesStarring: James Franco, Jonah Hill, Seth Rogen, Jay Baruchel, Danny McBride, Craig Robinson, Michael Cera, Emma WatsonWebsite: http://thisistheend.com/Sign up to receive updates, offers, and information from Machinima.http://bit.ly/MachinimaNewsletterFOR MACHINIMA'S BEST HIGH QUALITY SERIES, GO TO:http://www.youtube.com/subscription_center?add_user=machinimaprimeFOR MORE MACHINIMA, GO TO:http://www.youtube.com/subscription_center?add_user=machinimaFOR MORE GAMEPLAY, GO TO:http://www.youtube.com/subscription_center?add_user=machinimarespawnFOR MORE SPORTS GAMEPLAY, GO TO:http://www.youtube.com/subscription_center?add_user=machinimasportsFOR MORE MMO & RPG GAMEPLAY, GO TO:http://www.youtube.com/subscription_center?add_user=machinimarealmFOR MORE COMPETITIVE GAMING, GO TO:http://www.youtube.com/subscription_center?add_user=machinimavsFOR MORE ANIMATIONS & SHORTS, GO TO:http://www.youtube.com/subscription_center?add_user=happyhourFOR MORE TRAILERS, GO TO:http://www.youtube.com/subscription_center?add_user=machinimatrailerWANT TO JOIN THE MACHINIMA AFFILIATE PROGRAM? FILL OUT AN APPLICATION HERE:http://bit.ly/13ACBHg

  7. article Police Reports -- Week of June 9

    Wednesday, June 12, 2013 4:00 am

    Oro Valley

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  8. article (June 11) Today's Top Headlines - Top 10 stories of the day

    Tuesday, June 11, 2013 8:31 am

    1. OBAMA ACCEPTS NON-PRESCRIPTION DISTRIBUTION OF MORNING-AFTER PILL

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  9. article Dad, you deserve a break (Easy DIY projects that spruce up a home in no time)

    Monday, June 10, 2013 5:00 pm

    (BPT) - With Father’s Day right around the corner, give Dad a break from his “to do” list by taking care of the easier DIY tasks for him. From simple fixes to bigger projects, sometimes all you need is the right tool at the right time, to get the job done.

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  10. article State GOP lawmakers threaten to torpedo the budget

    Friday, June 7, 2013 1:20 pm

    PHOENIX -- Some GOP lawmakers are threatening to torpedo the budget being pushed by their own leaders if $400 million in planned spending is not cut across the board.

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  11. article Get smart about buying insurance

    Thursday, June 6, 2013 5:00 pm

    (BPT) - For most Americans, insurance coverage is a necessity. While coverage can be confusing and expensive to obtain, its solace is undeniable in the event of a car crash, emergency surgery or if your home has been damaged in a storm.

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  12. article (June 6) Today's Top Headlines - The Top 10 stories of the day

    Thursday, June 6, 2013 11:28 am

    1. NSA COLLECTS VERIZON PHONE RECORDS

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  13. article Enjoying Home Entertainment--Without The Techno Clutter

    Thursday, June 6, 2013 4:44 am

    (NAPSI)—The marriage of technology and entertainment has been a match made in heaven. The many things you can see, do and interact with through your home entertainment devices and flat-panel TV couldn’t even have been imagined a few years ago. Cable and satellite programming, gaming consoles, Blu-ray DVD players and other Internet-enabled devices are just some of the ways we all enjoy our magnificent, wide-screen TVs. It’s a beautiful thing.

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  14. article (June 5) Today's Top Headlines - Building in Pennsylvania collapses, many trapped, some feared dead

    Wednesday, June 5, 2013 9:17 am

    According to a USA Today report, As many as eight to 10 people are believed trapped in the rubble of two buildings that collapsed in central Wednesday in central Philadelphia.

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  15. article Here's hoping we have not wasted our heritage

    Monday, June 3, 2013 2:05 pm

    1992

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  16. article Tucson–Joe Bourne Returns to local church

    Friday, May 31, 2013 10:45 am

    Back by popular demand, popular local jazz artist has appeared with The Stylistics, Natalie Cole, The Pointer Sisters, and Dionne Warwick, and will present a free jazz concert in NW Tucson on Saturday, June 15, 7-9 pm.

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  17. article (May 31) Today's Top Headlines - The Top 10 stories of the day

    Friday, May 31, 2013 9:00 am

    1. AUTHORITIES INTERVIEW PERSON OF INTEREST IN RICIN CASE

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  18. article (May 30) Today's Top Headlines - The Top 10 stories of the day

    Thursday, May 30, 2013 9:49 am

    1. RICIN DETECTED ON LETTERS THREATENING NYC MAYOR BLOOMBERG

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  19. article Mountain View student looks at future in business, beauty

    Wednesday, May 29, 2013 4:00 am

    Highly driven to be successful in life, 18-year-old Ashley Doughty has used her last year of high school as a stepping-stone in pursuing her career choice of cosmetology.

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  20. article This Summer: Stay in shape without a gym membership

    Tuesday, May 28, 2013 11:38 am

    (StatePoint) It’s not as easy to hide under layers of clothing during the summer. You’ll want to look your best in those shorts, t-shirts and bathing suits; as such, staying in shape is key.

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  21. article (May 24) Today's Top Headlines - The stories of the day

    Thursday, May 23, 2013 8:19 am

    1. BOY SCOUTS ADMIT GAY YOUTHS, NOT ADULTS

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  22. article Got student debt? How your credit affects more than just borrowing power

    Wednesday, May 22, 2013 5:00 pm

    (BPT) - If you’re a recent college graduate, chances are you left school with more than just a diploma. You’re probably carrying debt, as well. You may already know how debt affects your future borrowing power, but it’s important to also understand how credit impacts other areas of your financial life, as well – such as how easily you’ll be able to rent an apartment when you leave home.

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  23. youtube TRAILER ---> Star Trek Into Darkness

    Wednesday, May 22, 2013 11:25 am

    http://www.joblo.com - "Star Trek Into Darkness" - Official Trailer Source: http://trailers.apple.com/trailers/paramount/startrekintodarkness/ In Summer 2013, pioneering director J.J. Abrams will deliver an explosive action thriller that takes Star Trek Into Darkness. When the crew of the Enterprise is called back home, they find an unstoppable force of terror from within their own organization has detonated the fleet and everything it stands for, leaving our world in a state of crisis. With a personal score to settle, Captain Kirk leads a manhunt to a war-zone world to capture a one man weapon of mass destruction. As our heroes are propelled into an epic chess game of life and death, love will be challenged, friendships will be torn apart, and sacrifices must be made for the only family Kirk has left: his crew. Official Site: http://www.StarTrekMovie.com Director: J.J. Abrams Cast: Chris Pine, Zachary Quinto, Zoe Saldana, Karl Urban, Simon Pegg, Anton Yelchin, John Cho, Bruce Greenwood, Benedict Cumberbatch, Peter Weller Writers: Alex Kurtzman , Roberto Orci , Damon Lindelof In theaters: May 17th, 2013 Copyright © 2013 Paramount Pictures

  24. article (May 22) Today's Top Headlines - 10 things you need to know today

    Wednesday, May 22, 2013 8:27 am

    1. OKLAHOMA BEGINS CLEARING TWISTER DEBRIS

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  25. article Five steps to create a customized outdoor living space with railing

    Tuesday, May 21, 2013 5:00 pm

    (BPT) - Railing can upgrade any deck from drab to fab – adding style, as well as safety and support. In fact, it’s often the one element that truly sets your outdoor living space apart from others in the neighborhood. Here are five steps to create the perfect perimeter for your deck.

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