Old drug may point the way to new treatments for diabetes and obesity

Feb. 10, 2013 ? Researchers at the University of Michigan's Life Sciences Institute have found that amlexanox, an off-patent drug currently prescribed for the treatment of asthma and other uses, also reverses obesity, diabetes and fatty liver in mice.

The findings from the lab of Alan Saltiel, the Mary Sue Coleman director of the Life Sciences Institute, are scheduled to be published online Feb. 10 in the journal Nature Medicine.

"One of the reasons that diets are so ineffective in producing weight loss for some people is that their bodies adjust to the reduced calories by also reducing their metabolism, so that they are 'defending' their body weight," Saltiel said. "Amlexanox seems to tweak the metabolic response to excessive calorie storage in mice."

Different formulations of amlexanox are currently prescribed to treat asthma in Japan and canker sores in the United States. Saltiel is teaming up with clinical-trial specialists at U-M to test whether amlexanox will be useful for treating obesity and diabetes in humans. He is also working with medicinal chemists at U-M to develop a new compound based on the drug that optimizes its formula.

The study appears to confirm and extend the notion that the genes IKKE and TBK1 play a crucial role for maintaining metabolic balance, a discovery published by the Saltiel lab in 2009 in the journal Cell.

"Amlexanox appears to work in mice by inhibiting two genes -- IKKE and TBK1 -- that we think together act as a sort of brake on metabolism," Saltiel said. "By releasing the brake, amlexanox seems to free the metabolic system to burn more, and possibly store less, energy."

Using high-throughput chemical screening at LSI's Center for Chemical Genomics to search for compounds that inhibit IKKE and TBK1, the researchers hit upon an approved off-patent drug: amlexanox. They then demonstrated that amlexanox had profound beneficial effects in both genetic and dietary-induced obese mice. The chemical lowered the weight of obese mice and reversed related metabolic problems such as diabetes and fatty liver.

"These studies tell us that, at least in mice, the IKKE/TBK1 pathway plays an important role in defending body weight by increasing storage and decreasing burning of calories, and that by inhibiting that pathway with a compound, we can increase metabolism and induce weight loss, reverse diabetes and reduce fatty liver," Saltiel said.

The drug has been on the market in Japan for more than 25 years.

However, the researchers don't yet know if humans respond with the same pathway, or if the discovery of amlexanox's effectiveness in mice can lead to a compound that is safe and effective for treating obesity and diabetes in humans.

"We will be working hard on that," Saltiel said.

Saltiel's search for a drug targeting the IKKE/TBK1 pathway was supported by the Life Science Institute's Innovation Partnership, which provides philanthropic funding and business mentorship to help move promising research toward commercialization.

The research was also supported by the National Institutes of Health, the Michigan Diabetes Research and Training Center, the Michigan Institute for Clinical and Health Research, and the Nathan Shock Center in the Basic Biology of Aging.

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Story Source:

The above story is reprinted from materials provided by University of Michigan.

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

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Journal Reference:

1. Shannon M Reilly, Shian-Huey Chiang, Stuart J Decker, Louise Chang, Maeran Uhm, Martha J Larsen, John R Rubin, Jonathan Mowers, Nicole M White, Irit Hochberg, Michael Downes, Ruth T Yu, Christopher Liddle, Ronald M Evans, Dayoung Oh, Pingping Li, Jerrold M Olefsky, Alan R Saltiel. An inhibitor of the protein kinases TBK1 and IKK-? improves obesity-related metabolic dysfunctions in mice. Nature Medicine, 2013; DOI: 10.1038/nm.3082

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/most_popular/~3/B9hZmGf5ZUs/130210143250.htm

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PFT: Suggs sees Flacco as Ravens' new leader

Getty Images

With the Patriots tepid on the topic of keeping cornerback Aqib Talib with a multi-year deal, his former college coach has offered a surprisingly strong assessment in response to the notion that Talib doesn?t work hard enough.

?[H]e loves to play football,? Mark Mangino recently told Jeff Howe of the Boston Herald.? ?He enjoyed practice time.? He hustled, made plays, did all of his drill work full speed, played hard in the games, did what was asked of him in the weight room, got bigger and stronger when he was with us.? I find that a little hard to believe.

?Things can change, obviously, but I stopped into the Tampa Bay Buccaneers training camp [last summer]. I visited with several members of the staff, front office people, strength coaches, trainers, assistant coaches. To the person, they told me what a great job Aqib was doing. ?He is showing leadership. He is working his tail off in the [OTAs].? He?s been a leader.? He is really busting his butt, and he is really working hard.?

?That doesn?t always happen. I have been to training camps in the past where I?ve had a former player that I?ve coached, and the coaches have come up to me and say, ?This player doesn?t work hard. He?s not into it.?? They?ll tell you the truth. When you go to these NFL places, they don?t mince any words.?

The Bucs may not have minced words, but they eventually traded Talib.? And it?s no surprise.? As coach Greg Schiano tries to build a roster of players of high character, Talib was one of several who simply didn?t fit.

That said, Talib possibly was working hard; it could be that his four-game suspension for violating the league?s policy regarding performance-enhancing substances prompted the trade.? And it could be that an Adderall-free Talib doesn?t work as hard as he does when taking the banned stimulant.

Still, it seems a little odd Mangino is singing Talib?s praises.? Throughout Talib?s various on-field and off-field struggles, Mangino has not been a particularly vocal defender.? Also, it was widely known during the weeks preceding the 2008 draft that Kansas coaches were not saying flattering things about Talib to scouts.

The question now for the Pats is whether they can strike a deal that will extend Talib?s stay beyond a handful of 2012 games.? If he leaves, they won?t have gotten much in return for the fourth-round pick they sent to Tampa.

But at least they got a seventh-round pick back in return.

Source: http://profootballtalk.nbcsports.com/2013/02/10/suggs-doesnt-think-hes-lewiss-successor-as-ravens-leader/related/

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The Best Text Expansion App for Mac

Strangely, Mac OS X has a wide variety of great text expansion apps and everyone does the job well. That said, TypeIt4Me is our favorite thanks to its comprehensive feature set, great performance, and reasonable price.

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• Type a short snippet that can expand to styled or unstyled text of virtually any length (and include pictures)
• Insert several types of variables into snippets, including date, time, other snippets, the clipboard, and more
• Create snippets that receive input from fillable forms
• Create snippet groups that respond to input in different ways
• Specify special behaviors for specific applications
• Easily back up your snippets to any folder
• Expand by typing or by choosing a snippet from the menu
• Invoke AppleScripts and shell scripts
• Reposition the cursor in a snippet so you're typing where you want to post-expansion
• Emulates key presses (e.g. tab, backspace, etc.)
• Import data from TextExpander, TypeIt4Me, and Automaton Typer

Despite the very low price for aText ($5), it's remarkably comprehensive. It offers mostly the same feature set as bigger apps like TextExpander for a fraction of the cost. Text expansion works as expected, you can specify when specific groups of snippets should expand, and you have the ability to include so many variables that one little snippet could, potentially, create a unique letter or document. If you use another text expansion app, there's a good chance aText imports its data. It doesn't cost much, it does practically everything, it's simple to use, and it's easy to switch from other popular solutions if you're interested.

While aText isn't short on features, one notable omission is the ability to sync snippets. While you can specify a backup folder, to which aText saves a backup of your snippets at a specified interval, you can't choose where it actually saves the original copy. This means you can't sync with services like Dropbox or Google Drive, making aText a somewhat less-desirable choice for those with multiple computers. Personally, I use it with two machines but find it a bit of a hassle to manually make the updates. That said, it's a small price to pay when you're already getting so much for such a small price. Additionally, Tran (the developer) tells me that syncing support is a forthcoming feature so it shouldn't be long until this isn't an issue at all.

TypeIt4Me ($5) was our former top pick. It packs quite a punch for $5, too, but doesn't offer as many variable options (like fillable forms) as aText. It does offer a number of unique features like autocorrect, however, so it's worth a look if you want something a little different from most of the competition at a very low price.

Text Expander ($35) offers a few more features than aText?notably sync?and a mobile app that's crippled by iOS' rules and restrictions. While TextExpander is a fantastic alternative?and, in some ways, better?it's not a better value than aText. You'll pay seven times more for a very similar experience.

Typinator (24.99?) offers a similar feature set to the other text expansion apps but its price has only gone up. While it is, at the moment, slightly cheaper than TextExpander it doesn't work quite as well. When filling out custom form variables, for example, if the form window loses focus (i.e. you click outside of it) it just disappears. I contacted the developer about this issue and was told it's impossible to fix. TextExpander doesn't have this problem, and when I found the same issue in aText its developer fixed it in less than 24 hours.

DashExpander (Free, $3 Premium) has an unusual interface and can be a little weird to use at first, but is nonetheless a solid text expansion app. It's also your only free option, so if you don't want to pay anything at all it's the only way to go. While we still really like it, when our first and second choices only cost $5 we highly recommend supporting these developers by paying such a small fee for their excellent work.

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Lifehacker's App Directory is a new and growing directory of recommendations for the best applications and tools in a number of given categories.

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You can follow Adam Dachis, the author of this post, on Twitter, Google+, and Facebook. ?Twitter's the best way to contact him, too.

Source: http://feeds.gawker.com/~r/lifehacker/full/~3/obnlPBiWKw4/the-best-text-expansion-app-for-mac

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Five crew killed in cruise ship safety drill

Nestor Perez / EPA

A rescue vessel (bottom L) is seen next to the overturned lifeboat (bottom R) of the 'Thomson Majesty' cruise ship (behind) at the pier where 'Thomson Majesty' cruise ship is docked at Santa Cruz de la Palma, Canary Islands, Spain on Feb. 10.

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By Sonya Dowsett and Teresa Larraz, Reuters

MADRID ? Five crew members died in an emergency drill on a cruise ship in the Canary Islands on Sunday, police said.

Cables snapped on a lifeboat and it plunged 65 feet to the ocean and fell upside down, killing the five and injuring three others aboard, during the mock rescue exercise on the Thomson Majesty, operated by British travel group TUI Travel. It was in the port of La Palma.

TUI, Europe's largest tour operator, did not respond immediately to telephone calls or email requests for comment.

Three of the dead were Indonesians. The other dead were a Filipino and a Ghanaian.

The Thomson Majesty, with five restaurants and two swimming pools, cruises to the Canary Islands, the Mediterranean and the Red Sea, according to Thomson's website.

Copyright 2013 Thomson Reuters. Click for restrictions.

Source: http://worldnews.nbcnews.com/_news/2013/02/10/16917861-five-crew-killed-in-cruise-ship-safety-drill?lite

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Seagal, Ariz sheriff train posses to guard schools

PHOENIX (AP) ? The self-proclaimed "America's Toughest Sheriff" is joining forces this weekend with action movie star Steven Seagal to train volunteer armed posse members to defend Phoenix-area schools against gunmen.

Maricopa County Sheriff Joe Arpaio announced the controversial plan in the wake of the December Newtown, Conn., school shooting that left 27 people dead, including the gunman and 20 first-graders.

The exercise is planned for Saturday at a closed school site in suburban Fountain Hills outside Phoenix where sheriff's SWAT members will act as shooters and 25 teenagers will play the part of students during mock scenarios involving up to three gunmen.

Seagal, best known for his roles in movies such as "Above the Law" and "Under Siege," will lead training on hand-to-hand defense tactics, among other techniques, drawing from his expertise in martial arts, according to a sheriff's office news release.

Arpaio's office didn't respond to requests for comment Friday, and Seagal representatives also did not return telephone messages from The Associated Press.

When faced with criticism in January about the school posse plan, Arpaio snapped back: "Why would people complain about my posse being in front of schools to act as prevention?"

He boldly announced the plan on the grounds of an elementary school, saying at the time he wanted the patrols publicized.

"I want everyone to know about it for the deterrence effect," Arpaio said, adding that no taxpayer money would be spent on the patrols and volunteers will be supervised over the radio or telephone by actual deputies.

Arizona Democratic House Minority Leader Chad Campbell called the plan to use Seagal as an instructor "ludicrous."

"Steve Seagal is an actor. That's it. Why don't we also have Clint Eastwood and Chuck Norris and Bruce Willis come out and train them too while we're at it," Campbell said.

Campbell has been a vocal critic of Arpaio's school posse protection plan, complaining that using untrained, armed civilians to protect students is a bad idea and likely will only make the facilities more dangerous.

"He's making a mockery out of it. You're having a movie actor train people how to protect schools?" Campbell said.

Randy Parraz, president of Citizens for a Better Arizona, also a longtime Arpaio critic, said it's unfortunate the sheriff, known nationally for his tough stance on illegal immigration, is using the "wake of a tragedy like Newtown" to grab headlines.

"We'd like to think he would take something like this much more seriously," said Parraz, who added that his group planned to be at Saturday's event with petitions to recall Arpaio.

The patrols were launched at 59 schools in January throughout unincorporated areas and communities that pay Arpaio's agency for police services. The sheriff announced this week he needs more members to continue the patrols, calling for 1,000 additional citizens to step up and volunteer.

Current posse members already are used to bolster the sheriff's office force by providing police protection at malls during the holidays, directing traffic and transporting people to jail.

Arpaio even sent one group of posse members to Hawaii to conduct an examination into the authenticity of President Barack Obama's birth certificate.

Joselyn Wells, a mother of three children at a school in suburban Phoenix, where Arpaio's posse has begun patrolling, said she was excited to hear about the initiative.

"A lot of people sit around and watch these things happen, watch key signs and no one wants to do anything about it," she said when Arpaio announced the plan. "Nobody wants conflict, nobody wants to be out in the limelight. And he doesn't care. He wants to do the right thing."

Andrew Sanchez, however, a town council member in Guadalupe, said he wants nothing to do with posse members patrolling schools in his community, which spends about $1.2 million annually for Maricopa County sheriff's patrols.

"We are paying him to have certified deputies here, not to bring a circus and not to use our town as a political platform," Sanchez has said.

The volunteers, dressed in uniforms and driving patrol vehicles, some authorized to carry guns after training, won't go onto school grounds unless they spot danger, but will instead patrol around the facilities, Arpaio said.

Seagal is already a volunteer posse member in Maricopa County, and has been deputized with sheriff's offices in New Mexico, Texas and Louisiana, where a film crew followed the actor on ride-alongs with Jefferson Parish sheriff's deputies for the reality TV show "Steven Seagal: Lawman."

Arpaio says other notable people also have joined his more than 3,000-strong volunteer armed posse, including "The Incredible Hulk" star Lou Ferrigno and actor Peter Lupus of TV's "Mission: Impossible."

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Online: http://www.mcso.org/About/Posse.aspx

Source: http://news.yahoo.com/seagal-ariz-sheriff-train-posses-guard-schools-165630582.html

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NBR interviews Steve McIntyre: hard-hitting business journalism or ...

The National Business Review (NBR) is New Zealand?s biggest selling business weekly. This weekend it published a profile of Steve McIntyre, the ClimateAudit blogger and amateur statistician who has long had an unhealthy obsession with hockey sticks. Here?s how it introduced him on the web version of the article:

A man who has become the arch-enemy of climate scientists for exposing serious flaws in a United Nations study on global warming believes the issue has been greatly overstated.

Vilified by global warming zealots, Canadian Steve McIntyre, who was passing through Auckland this week, told NBR ONLINE the impact of global warming is likely to be ?about half? of what current scientific models are showing.

Unpacking all the errors and misrepresentations in just those two opening sentences is a major task, so I?ll restrict myself to a few bullet points:

• McIntyre has pissed off a few paleoclimate people (Mike Mann in particular), but is no ?arch-enemy? of an entire discipline.
• He exposed no substantial flaws in any study, though he has tried hard to create that impression. The sum total of his efforts has done nothing to change our understanding of paleoclimate.
• The United Nations doesn?t do climate studies. The UN and WMO coordinate the IPCC, which summarises all the science done in academic institutions around the world.
• McIntyre?s main contribution to science has been to orchestrate and agonise over freedom of information requests sprayed around the climate community, especially the Climatic Research Unit at the University of East Anglia, and thereby to waste a huge amount of real scientists? time.
• McIntyre lacks any credible expertise that would allow him to sit in judgement on the likely impact of a warming climate.

The NBR article continues:

Mr McIntyre, who is a mathematician and former mining company executive, says ?the onus is on the people arguing it?s a big problem to really show in an engineering quality report why it?s a big problem?.

More to the point is that McIntyre has been up to his elbows in organised efforts to delay action on climate change for at least the last ten years, as DeSmogBlog?s record of his activities shows ? but you wouldn?t guess that from the fawning interview by Rod Vaughan.

The really jaw-dropping moment, however, is when Vaughan presents McIntyre?s views on climate impacts:

Asked how much damage has been caused to the environment so far from global warming, he said:

[?]?Activists will tend to say that carbon dioxide emissions in the last 50 years have caused serious negative impacts.

?But from my point of view I would say I don?t know what they are and certainly on balance there?s been no serious impact.

There?s none so blind as those who won?t look at the Arctic, glacier retreat, increasing extreme weather events, or any of the many other signs of a rapidly changing climate system. McIntyre has made no contribution to the study of climate change, but he has made a huge contribution to the campaign to do nothing about it. His wilful ignorance, and his willingness to present it as wisdom, makes for unedifying reading. More?s the pity, then, that the NBR should choose to feature McIntyre?s piffle as worthy of its reader?s attention.

Climate change is already the biggest challenge the business community will have to face over the next century. Dealing with the impacts of climate change ? from extreme weather events to shifting climate zones and ocean acidification ? is going to be tough. Creating an economy in which business can thrive at the same as radically reducing emissions is an urgent necessity. It can?t be dismissed by the arm-waving of mining consultants with a political axe to grind.

It could be argued that the business community gets the journalism it deserves. On the basis of this dreadful and fatuous interview, it would appear New Zealand?s business community is in deep, deep trouble.

Tagged as: ClimateAudit, Michael Mann, NBR, Nevil Gibson, Steve McIntyre

Source: http://hot-topic.co.nz/nbr-interviews-steve-mcintyre-hard-hitting-business-journalism-or-fatuous-piffle-you-decide/?utm_source=rss&utm_medium=rss&utm_campaign=nbr-interviews-steve-mcintyre-hard-hitting-business-journalism-or-fatuous-piffle-you-decide

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Explosive Power of Combustion Makes Floppy Little Silicone Robot Jump [Video]

A simple chemical reaction is used to power a robot's lofty leaps. Applications could be search-and-rescue operations

By Katharine Sanderson and Nature magazine

Image: Shepherd, R. F. et al. Angew. Chem. Int. Edn Engl.

From Nature magazine

Kaboom! Controlled explosions in the legs of this silicone 'soft robot' make it leap higher than 30 times its own height.

Researchers led by George Whitesides, a chemist at Harvard University in Cambridge, Massachusetts, have engineered a three-legged silicone device that is powered by combustion ? previously used only in hard systems such as diesel engines.

The soft robot has in each of its legs a channel with a soft valve at the end. Methane and oxygen gases are fed into this channel in a ratio of one part methane to two parts oxygen. The computer that controls how much gas is let in also controls a high-voltage cable connected to electrodes in each leg.?

When the computer sparks the electrodes, the methane and oxygen explode, turning into carbon dioxide and water ? and releasing a lot of energy. The downward force from the explosion makes the robot jump ? higher than 30 centimetres so far, although the researchers say the range has been limited by the height of the testing chamber. The soft valve is crucial, says Robert Shepherd, a study co-author and engineer at Cornell University in Ithaca, New York. It closes in response to high pressure, thus making the pressure even higher, and then it opens after the explosion to let the exhaust gases out.

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Soft robots are lighter and simpler than hard systems, and they are relatively inexpensive to produce ? but they have previously been limited to compressed-air power, owing to the high heat generated in combustion reactions. ?The key discovery is that this material can work at these high temperatures,? says Shepherd. The robot has withstood more than 30 consecutive explosive jumps so far. The results were published this week in Angewandte Chemie.

The researchers hope that a developed version of their device could be used for search-and-rescue operations, leaping and cartwheeling its way over any obstacles that might block its path.

This article is reproduced with permission from the magazine Nature. The article was first published on February 8, 2013.

Source: http://rss.sciam.com/click.phdo?i=8b16a447ce6f7925ddc412f2f333370a

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