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June 19, 2013
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      • posted: June 19
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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 Avoiding Tick Dangers This Summer

    Tuesday, June 18, 2013 7:04 am

    (NewsUSA) - Tick-borne illnesses are found throughout the United States. Though Lyme disease, transmitted by blacklegged ticks, is the most pervasive and publicly discussed, the Centers for Disease Control and Prevention (CDC) lists a wide range of diseases spread by ticks. With tens of thousands of people impacted each year from such illnesses, the National Pest Management Association (NPMA) advises summer enthusiasts about the danger of disease transmission from ticks and encourages them to take proper precautions to protect against exposure to these blood-sucking pests.

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  3. article Community needs, solutions vie for spot in future county bond package

    Monday, June 17, 2013 9:54 am

    When the community was asked to identify priorities to take to voters in a potential November 2014 Pima County bond election, the result was approximately $1.3 billion worth of projects.

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  4. article Celebrate the dairy days of summer by keeping products cool and fresh

    Sunday, June 16, 2013 5:00 pm

    (BPT) - Nothing says summer like dairy products from the number one dairy state, California. From scoops of cold, creamy ice cream to melted cheese atop juicy grilled burgers, dairy and summer menus go together like sweet corn and butter. But nothing spoils the summer fun like spoiled milk, which is why it’s important to know how to store your dairy products – especially in the hotter months.

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  5. article Gadget Magnet - Data Doctors on dealing with dead pixels

    Saturday, June 15, 2013 4:15 am

    Q: What causes a laptop’s screen to suddenly have a tiny black spot in the middle of it and is there anything I can do about it? — Thomas

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  6. article (June 14) - Today's Top Headlines - The top 10 stories of the day

    Friday, June 14, 2013 9:47 am

    1. OBAMA APPROVES ARMING REBELS

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  7. article Such the Spot - Please don't feed the children

    Friday, June 14, 2013 4:00 am

    I have a pet peeve. Who am I kidding? I have many of them, actually, but today I’m focusing on just the one. It pertains to my children. Here’s the scoop: I’m really fed up with people offering food to my children (pun totally intended). It happens all of the time. At church, for example. My children attend Sunday School while my husband and I are in the congregation at church. The service—and subsequently, Sunday School lessons—last an hour. One hour. The 10:30 a.m hour, at that. On any given Sunday, my family will typically enjoy a fairly hearty weekend treat of a breakfast. Waffles or pancakes or biscuits and eggs. By the time we drop the kids off in their respective Sunday School classrooms, scarcely an hour has passed since my family sat down for breakfast. Yet, when we pick them up from Sunday School, we hear reports of snacks that were given out. And I’m not talking about something healthy like a handful of grapes or a segment of orange. I’m talking about powdered donuts or cookies or packaged cereal bars—food imposters laden with sugar and preservatives.

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  8. article Budget-friendly ways to refresh old outdoor spaces

    Thursday, June 13, 2013 5:00 pm

    (BPT) - Indoors or outdoors, your home decor needs some TLC to look its best. Replacing worn or dated furniture or flooring inside your home is considered fairly easy. But when outdoor spaces start to appear shabby, do you decide to live with the tired look because you think freshening the space will be too time-consuming or costly?

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  9. article Bright ideas to get your home guest ready

    Thursday, June 13, 2013 5:00 pm

    (BPT) - Summer has arrived and vacation season is underway. With the kids home from school, and family and friends anxious to visit, you can expect the stress of getting your home ready to be in full swing. Here are a few helpful tips that will make you a successful host and give your guests a warm welcome.

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  10. article What's Up UA? - Supernova Discovered at UA SkyCenter

    Thursday, June 13, 2013 10:53 am

    Now you see it – now you don't. This, in a nutshell, describes how Adam Block, renowned astrophotographer and astronomy educator with the University of Arizona's Mt. Lemmon SkyCenter, discovered a supernova in a galaxy far, far away.

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  11. 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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  12. article Seniors Serve Town By Serving Breakfast

    Thursday, June 13, 2013 4:44 am

    (NAPSI)—A group of seniors with imagination and initiative recently demonstrated how committed volunteers can make a difference in a community.

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  13. article A Surprising Solution To Migraine Pain

    Thursday, June 13, 2013 4:44 am

    (NAPSI)—The next time you get a headache, you might care to consider this: If you’re like most migraine sufferers, you don’t even know it, and even if you do, you may not be treating it properly to get the fastest relief.

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  14. article Ask the pharmacist: How to avoid medication misfortune during a natural disaster

    Wednesday, June 12, 2013 5:00 pm

    (BPT) - Whether it’s plywood, bottled water or generators, Americans gather the necessary supplies and seek the appropriate shelter if confronted by the wrath of Mother Nature. Regardless of the disaster – hurricanes, tornadoes, wildfires – lives can be turned upside-down in an instant. Some of the most commonly overlooked items, as people stock up for emergencies, are prescription medications. In some cases, not having access to necessary medication can itself be a life-threatening situation.

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  15. article Hitting the road? Apps to pack to avoid summer brain drain

    Wednesday, June 12, 2013 5:00 pm

    (BPT) - Warm weather and sunshine are putting families across the country in vacation-planning mode. Whether traveling by train, plane or automobile, mobile devices are typically the first thing parents and kids pack.

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  16. IRHS Summer Basketball

    Ethan Tees, a fifth grader, shoots the ball in the spot game at the Ironwood Ridge basketball camp.

  17. IRHS Summer Basketball

    DoriaRose Lukasik-Dresch, a third grader, gets ready to shoot the ball during the spot drill.

  18. article Add years to your pet's life with expert tips

    Tuesday, June 11, 2013 5:00 pm

    (BPT) - Few things in life are as special as the unconditional love and loyalty a pet provides. With 78.2 million owned dogs and 86.4 million owned cats in the United States, according to The Humane Society, it’s obvious Americans enjoy having pets. What might not be so apparent is how best to care for them. When it comes to making sure your pet stays healthy and lives as long as possible, what steps can you take?

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  19. 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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  20. article Disciplined and committed candidates wanted to serve in the elite United States Submarine Force

    Monday, June 10, 2013 5:00 pm

    (BPT) - Sailors silently gliding underwater while patrolling the ocean depths in a nuclear-powered sub and the pride of earning the coveted Submarine Dolphins. This is the exciting and challenging life for personnel in the United States Naval Submarine force.

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  21. article Such the Spot - A personal plea for water safety awareness

    Monday, June 10, 2013 8:54 am

    This time of year gets to me. When the mercury climbs and the sun won’t relent, my mind goes back. It was on a midsummer day nearly four years ago that my then two-year-old son nearly drowned. I took my four children to a friend’s house to spend an afternoon cooling off in their pool. My friend and I sat in the shallow end of her pool keeping watch as our combined six children splashed and swam the day away. My two-year-old stayed at my side on the pool’s lagoon, spraying the other kids with a stream from a water gun he’d taken a liking to.

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  22. article Step carefully this summer: Prevent common foot cancers

    Sunday, June 9, 2013 5:00 pm

    (BPT) - Common cancers have a high level of awareness among Americans – and rightly so. Prevalent cancers like breast, colon or prostate affect a large number of people, and it’s important to be aware of preventive and diagnostic measures. But cancer can also strike in an area of the body many people don’t think about – the feet.

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  23. article Such the Spot - When used car negotiations go awry

    Thursday, June 6, 2013 11:34 am

    My eighteen-year-old daughter’s beloved first car broke down on the side of I-10 about a month ago. In order to buy that little green Volkswagen Beetle in the first place, she’d saved for well over a year, stashing away every penny she earned from her part-time job, as well as cash birthday and Christmas gifts. So when the temperature gauge somersaulted and grey smoke poured from the exhaust pipe that day, my daughter’s dream car quite literally went up in smoke. And, unfortunately, there were no affordable options to get it back up and running. There was a grieving process to be sure, but perhaps the heaviest burden fell on the shoulders of my husband. Used car shopping, you see, is like the kryptonite to his Superman.

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  24. article What's Up UA? - Brigetta Barrett Named Pac-12 Woman of the Year

    Thursday, June 6, 2013 9:14 am

    The University of Arizona's Olympic silver medalist high jumper Brigetta Barrett has been named the Pac-12 Conference Woman of the Year for the 2012-13 academic year, Pac-12 Commissioner Larry Scott has announced.

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  25. article Help Fight Childhood Hunger When School Is Out

    Thursday, June 6, 2013 4:44 am

    (NAPSI)—For kids, summertime should mean food, friends and fun. For many families fighting to make ends meet, however, summer can mean struggling to stretch tight food budgets even further.

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  • Oro Valley Town Talk: What is and why is a General Plan?

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