There have been remote-controlled cyborg bugs before ? but now, possibly for the first time, you can tell a cockroach what to do via Twitter. Commands seem to consist mainly of "turn left" and "turn right," and it can only accept one command every 30 seconds. Plus it's only connected for short periods at a time. But still ? at last, someone who will pay attention to my tweets, no matter what. [Animal New York]
Source: http://io9.com/5972148/cyborg-cockroach-does-what-you-tell-it-on-twitter
Not Getting Sufficient Traffic To Your Web Page? Try out These Search Engine Optimisation Suggestions
For a enterprise to grow and become productive through the web, it should initial try to industry alone and achieve the market it wishes to target. To accomplish this, the best way happens to be search engine marketing. This can be a difficult advertising strategy due to all the options that this provides newcomers. Adhere to some elementary approach rules and you will find a better rate of success.
Search engines like yahoo give websites that routinely revise with refreshing content material greater search positions than websites which tend not to update or upgrade infrequently. To acquire on the top of search engine listings, it?s essential to also have new content material related to your blog with many different a similar keywords applied throughout your website.
Why should your small business use search engine marketing? Search engine optimization is undoubtedly an best strategy to primary website visitors to every single site of your website, rather than the website. To put it differently, you can use frequently used key phrases, as a way to primary traffic to other regions of the internet site. Those who are not searching for your small business especially, could find the end result intriquing, notable and be motivated to understand the rest of your backlinks.
A significant tip to remember in terms of search engine optimisation, would be to choose a keyword term that is ONLY 2 or 3 words long. Studies show that practically 60% of keyword words consist of two are three words and phrases so this will enable you to achieve the highest possible outcomes.
A good hint for ideal search engine marketing is always to write your internet site duplicate for people to see. To put it differently, it will you not good to try and cheat towards you to the top of search results by only positioning search phrases in proper areas. Search engine listings are smart adequate to acknowledge this strategy.
To prevent waiting around for Yahoo and google to include your website to its directory site, place a hyperlink to your website on increased rating sites. 1 good way to accomplish this is always to sign up in a well-known discussion board and will include a hyperlink for your web site within your signature. When Google tests the community forum, they?ll view your site and commence adding its internet pages.
These are merely several great approaches to create the building blocks of your successful empire. They ought to be adopted even when you have developed to the CEO of the million $ firm. It is because SEO will almost always be an effective and growing strategy to advertise your firm that could maintain your enterprise profitable in even hardest cost-effective times.
Thanks for reading. For more SEO tips and advice please visit digital composure
Source: http://www.barterforcash.com/not-getting-sufficient-traffic-to-your-web-page.html
Evernote Business
Evernote has taken its very popular note-taking organization app and made a version especially designed for small and medium-sized businesses. The new Business version of Evernote adds tools to help businesses be more productive and collaborative, such as the ability to access, use, manage and modify any Business Notebook and its contents, while Personal Notebooks stay private. Evernote Business administrators have the ability to invite and manage users, store research, presentations, documents, notes and more. You can even save entire webpages with the Evernote Web Clipper.
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You might have come across the two words 'physical therapy' already, but until now you have zero knowledge what it is. Then today is your lucky day because you can read everything about physical therapy below.
Physical therapy is actually a treatment procedure that's aimed at curing particular medical conditions and stopping them from ever occurring again. Physical therapy achieves this through promotion of body strength, function, movement and by concentrating on the muscles, nerves, and other systems of the body.
Physical therapy can actually be further subdivided into several types. First is orthopaedic physical therapy which takes place in the hospital after a patient has undergone surgery. Then there?s paediatric physical therapy which assists infants, children and adolescents in improving their gross and fine motor skills, strength, cognitive functioning and balance. Thirdly, there's geriatric physical therapy which involves helping older individuals who are having troubles because of aging.
Then there's neurological physical therapy that's aimed at helping individuals who are have neurological disorders like cerebral palsy, brain injuries, spinal cord injuries and many others. Heat physical therapy is yet another type that utilizes heat to relax and heal stiff joints and muscles. Lastly there's speech therapy which is for children with speech difficulties and for those who have problems with eating and swallowing.
Now that you know the different types of physical therapy, you must now learn about its benefits. Number one advantage is that physical therapy can pave the way for an individual to become normal again and be free of any pain and ailments like back pain New York or sciatica NYC. Physical therapy can also assist an individual who has been immobile to gain some amount of movement and flexibility. Additionally, this method of treatment also betters the overall health and fitness of the patient. Physical therapy also assists children with developmental problems and muscle and joint weaknesses perform better.
All of the above physical therapy benefits can be experienced only by a patient who keeps a bright and hopeful outlook in life. Additionally, he or she must always do what the therapist asks of him or her.
So do you want to try out physical therapy? Then, try out best physical therapy NYC where you?ll get supreme New York physical therapy that you can?t find in any other centres of physical therapy New York City.
Source: http://gserver.sampos.ch/wiki/index.php/Benutzer%3ARubensteinMoores462
Which means you can?t just replicated the revenue strategy of various other marketing expert inside your area of interest and expect so that it is productive. Regardless of the organization you signify, you can find primary truths that will assist enhance your marketing plan. total product blueprint review
Post brief e-textbooks on web sites that enable you to talk about files. This will likely flaunt your knowledge, entice visitors, and curiosity potential buyers with your web site. Ensure that your papers features many backlinks that viewers can make use of to achieve your web site.
When trying to cultivate an associate system to promote your product, think of providing your prospects the opportunity to grow to be affiliate marketer sellers. Once they invest in a product, you can existing them with the opportunity to grow to be an associate too. By giving a consumer the chance to affiliate marketer together with you, you might draw in a lot more enterprise. This will boost your income significantly, and also get you to an improved affiliate marketer marketer. brendon burchard
Think about carefully the kinds of items your backlinks bring about just before utilizing. When studying the best places to location affiliate backlinks, you ought to see revenue ?roll in.?
Another essential part of internet affiliate marketing is to get an numerous flow of back-links to your site. Nonetheless, you should be aware of links which lead to information that will deceive your visitors. An individual seeking notebooks will probably be an unsatisfied camper in the event you brand your weblink ?Laptop computers? but cause them to feline toys. Even if your strategy right behind the move is reasonable, your clients will really feel tricked from this mismatch between links and webpages. Feather hair extensions
To be productive with affiliate marketing online you must be informed about your target audience. Prospective customers are definitely the primary goal so you have to ensure their demands are achieved. Realise why your readers are going to your website in the first place. What is getting their focus?
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When someone is visiting your web site for sports information, that?s what they?re enthusiastic about locating. Placing a link for the affiliate website won?t offer you any gain unless of course it relates to sports. Website visitors display greater click-by way of costs on hyperlinks that are related to anything they came to learn about.
Showing that you will be a legitimate internet affiliate marketing expert requires some proper finesse. A subtlety is essential when putting back links. Take care to communicate the message to clients that you will be a company ?affiliated? together with the items.
Limit your business transactions to only acceptable and magnanimous organizations. A ample clients are the one that doesn?t offer you less than twenty percent commission payment on each and every item that you offer. Your time and energy will probably be compensated having a better spend if your small business is one who identifies your work.
In case you have picked the merchandise you want to offer for affiliate marketer lovers, make certain your advertising and marketing endeavours give attention to tugging in an correct audience for all those goods. Inexpensive goods can skate by with high-volume level, reduced-simply click-via methods. Costly goods require extreme, concentrated marketing in order to increase the buyer vs . site visitor ratio.
Bring in the proper viewers for the chosen affiliate marketer items. Should you be promoting low-cost items, you may use strategies directed for big viewers, however with low conversions. Recall that you would like customers rather than just internet browsers, so more expensive items could very well call for a much more centered hard work.
1 crucial part of affiliate marketing is the opportunity to get back-links in your website. It is recommended, nonetheless, to make certain that the links don?t get individuals to information that they weren?t wanting. A good way to get rid of a customer is usually to irritate them by hitting backlinks to information they are certainly not thinking about don?t provide these to your site selling Apple inc products should they be looking for a Personal computer. This mismatch in between the information of your advertising and marketing along with the information of your own website will shut down potential prospects.To improve your prospective earnings with affiliate internet marketing make sure to take into account the various forms of media that you can use. By giving folks all the info as you can, you increase the possibilities of them acquiring the goods that you will be marketing. Go in-level in your product or service overview. Involve information on how you apply the product or service plus the final results you have attained.
To acquire greatest publicity, use affiliate marketing online to promote your product or service. Considering these ideas you may be greater familiar with affiliate marketing online.
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Finding a graduate job is not as easy as finding a minimum wage position that requires no formal training. You will have to work harder to find a graduate job, but you will be rewarded with a position that you like, and that pays you well for the work you do.
The first tip to finding a graduate job is to have a good resume to hand out when you are on your job search. If you apply for a minimum wage job doing menial labor then you will walk into the place of business and fill out a job application that the business representative hands you. They do not want to know anymore about you than what is on their application. You do not need to have a resume for these types of positions. Companies that are looking to hire someone with a degree or with specialized skills and training expect a resume outlining all of your education, all of the skills you possess, all of your past employers, what your interests are, what you do in your spare time, and what charities and foundations you are affiliated with.
When you are looking for a graduate job you will look in places like the classified ads in newspapers, and you can look on bulletin boards that announce openings, and you can talk to friends and family to see if the companies they work for could possibly be hiring, and you can call employment agencies to help you find available positions.
Looking for a graduate job with an employment agency can be the most beneficial way to search for these positions. When you hire an agency to help you procure employment they will take down all of your information, and they will get a copy of your resume. Then they will go to work looking for career opportunities that fit your skills. These agents will often have knowledge of openings that no one else is aware of because the company that is hiring may use the same agency.
When you use an employment agency to help you locate the right job you can even begin to search for employment opportunities before you graduate from college. You can tell the agent when you will receive your degree and they can set up interviews and possible job connections before you actually graduate. Some companies even prefer to hire people who are about to graduate so they can get some of the brightest young minds that have yet to be tainted with rules and regulations of other establishments.
A graduate job is one step in the right direction so that you can secure a financial future for yourself. You can also have work that you like to do rather than just working to pay the bills. If you have been considering furthering your education so that you will be qualified to apply for one of these positions you need to go ahead and start right now. If you have the education then you need to start applying and sell yourself and your abilities now.
A graduate job may be harder to find than a manual labor position would be. Using an employment agency to help you find the right graduate job is the easiest way to accomplish this task.
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Source: http://businesscareerslist.blogspot.com/2012/12/tips-on-finding-graduate-job.html
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LONDON (AP) ? Financial markets were largely steady in holiday-thinned trading Monday though concerns remain over the progress of U.S. budget discussions and the future of the economic reform program in Italy.
For weeks, the discussions between the White House and Congress over a budget deal have been the main driver in markets. If a deal isn't agreed to by the start of 2013, automatic spending cuts and tax increases worth hundreds of billions of dollars will be imposed ? which many economists think could push the U.S. economy back into recession.
The prevailing view has been that a deal would be agreed to in time but as the deadline nears there are growing doubts over whether the U.S. will be able to avoid the so-called "fiscal cliff."
"The reality is given that the U.S. government is now closed for the holiday break the likelihood of anything other than soothing procrastination is highly unlikely much before the Jan. 1 deadline," said Michael Hewson, senior market analyst at CMC Markets.
Doubts over the progress of discussions prompted a fairly sizeable sell-off last Friday though many analysts still think there will be agreement on some sort of short-term measures.
"Even if this stopgap measure is implemented it may not be enough to prevent unwanted volatility in equity markets going into 2013 as investors try and assess the adverse impact on the U.S. economy," said Neil MacKinnon, global macro strategist at VTB Capital.
Most markets across Europe are only open for half a day and will only re-open again on Thursday. German markets are closed for Christmas Eve.
With around an hour of trading to go, Britain's FTSE 100 index of leading British shares was up 0.2 percent at 5,952 while the CAC-40 in France was down an equivalent rate at 3,655.
Wall Street was poised for more marked falls at the open in what will also be a holiday-shortened trading day ? both Dow futures and the broader S&P 500 futures were down 0.4 percent.
As well as monitoring developments in the U.S. over the coming days, investors will be keeping a close watch on what's going on in Italy ahead of a general election in February.
Over the weekend, outgoing Prime Minister Mario Monti indicated that he would be willing to return to the role if pro-reform parties back him.
Over the past year or so, Monti and his technocratic government have won plaudits in the markets for their economic reforms and efforts to get a grip on the country's borrowing. Italy has the second-highest debt burden among the 17 EU countries that use the euro. Only Greece's is higher.
Earlier in Asia, Hong Kong's Hang Seng, closed up 0.1 percent at 22,531.51 while South Korea's Kospi rose less than 0.1 percent to 1,981.82. Japanese markets were closed for the Emperor's birthday holiday.
Other financial markets were subdued too. In the currency markets, the euro was up 0.2 percent at $1.3227 while the benchmark New York oil price was down 3 cents at $88.63 a barrel.
Source: http://news.yahoo.com/markets-flat-holiday-thinned-trading-113231334--finance.html
By Alex Girda, Associate Editor
Nedbank Corporate Property Finance, a Durban-based financial organization, has reportedly provided a Pretoria developer with crucial financing that will be used in the development of two properties. Octodec Investments, a local developer, is working on phase two of the Tiny Town development, a residential and retail project that currently has a 2014 completion date attached. The other project Octodec is working on is the Cambridge Shopping Centre, a commercial development in the city?s central business district. The amount that Nedbank Corporate Property Finance has provided comes in at around $11.5 million, or 100 million South African rand.
Tiny Town was originally conceived in 1929 when it was meant to become an artist?s colony and included a number of residential units and a common garden. Tiny Town was then renovated in 2009 to meet modern expectations, while the overall direction of the area was rebranded while keeping in mind the space?s history and setting. Phase II will include 116 new for-rent residential units. Located in close proximity to the country?s seat of government, the new development will cater to a more exclusive type of resident in terms of its residential component. The project is currently in the town planning stage of development.
The Cambridge Shopping Centre will be located at the intersection of Struben, van der Walt and Bloed streets, in the north-western edge of the city?s central business district, in the immediate vicinity of the Pretoria Zoo, the largest in the country. The retail development already has an anchor tenant in place, in the Cambridge Foods grocery store. The Massmart Group-owned store has signed a ten-year leasing deal at the facility. Not counting the space that Cambridge Foods will be taking over, the retail center will have 11,100 square feet of leasable space, divided into 12 shops. The retail units will feature areas between 516 square feet and 1400 square feet. Some of the other residents of the Cambridge Shopping Centre are already in place, with another large national tenant on the roster being Cash Crusaders. The retail development currently has an attached opening date of February 2013.
Pretoria is one of three capital cities that represent the South African country, the city being the executive capital, making it the de facto capital of the state. It is located in the Gauteng province and has a population of around 500,000.
Source: http://moviesblog.mtv.com/2012/12/21/david-chase-not-fade-away-2/
Dec. 20, 2012 ? People with Type 2 diabetes have two to four times the risk of cardiovascular disease compared to people without the disease. The best way for doctors to predict which diabetes patients are at the greatest risk for heart disease is to use a coronary artery calcium (CAC) test in addition to the most commonly used assessment tool, according to researchers at Wake Forest Baptist Medical Center.
Current medical guidelines recommend treating all diabetes patients as high risk, but the Wake Forest Baptist study found that CAC can identify diabetes patients who are at very high risk for developing potentially fatal cardiovascular disease, as well as those who are at low risk. "Our observations challenge accepted medical knowledge that all people with diabetes have the same risk. CAC is key in predicting the specific risk level," said Donald Bowden, Ph.D., professor of biochemistry at Wake Forest Baptist and senior author of the study, which is published online in the December issue of the journal Diabetes Care.
"People at very high risk are 11 times more likely to die from cardiovascular diseases as compared to those at low risk. Diagnosing a more precise risk level should help doctors provide more effective treatments and hopefully improve outcomes," he said.
The community-based Diabetes Heart Study was designed to determine if CAC provided additional information about cardiovascular disease and mortality beyond the Framingham Risk Score, the most commonly used assessment tool. A total of 1,123 people with Type 2 diabetes between 34 to 86 years old were followed for an average of 7.4 years. The study participants were recruited from clinics in western North Carolina and reflect a cross section of families with diabetes-affected members in the region.
CAC uses a CT scan to detect calcium build-up in the arteries of the heart. According to Bowden, the cost of the test is relatively low and the radiation exposure is about half of what someone would get in a year "by just walking around."
"Based on our study, we think that CAC should be added to the Framingham tool as the standard of care for all people with diabetes," Bowden said.
The Wake Forest Baptist team hopes to conduct additional research on how adding CAC as a diagnostic tool for diabetics could affect treatment and outcomes.
Co-authors of the study are Subhashish Agarwal, M.D., of Oakwood Hospital and Medical Center; Neal Jorgensen, M.S., of the University of Washington; Amanda Cox, Ph.D., David Herrington, M.D., Jianzhao Xu, B.S., Barry Freedman, M.D., and J. Jeffrey Carr, M.D., of Wake Forest Baptist.
This study was supported in part by the General Clinical Research Center of Wake Forest Baptist Medical Center; National Institutes of Health grant R01-AR48797, and National Heart, Lung and Blood Institute grants R01-HL67348 and R01-HL092301.
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NY Giants Victor Cruz and The Meat House General Manager Craig Jacobson
The Meat House of Roslyn, N.Y., the North Shore's newest butcher and purveyor of fine meats and prepared foods, joined forces with Steiner Sports, the country's leading producer of authentic hand-signed collectible memorabilia, as Steiner Sports celebrated its 25th anniversary and raised money for select charities including Hurricane Sandy Relief efforts.
"When Brandon Steiner called to see if we would like to help out one of the days of his fundraising event the answer was not what but when and where!" says Meat House general manager and operations partner Craig Jacobson. As part of the three day event, The Meat House generously donated its services and provided catering, including their signature marinated barbecued meats for an illustrious list of legendary athletes, staff and VIP guests including Mariano Rivera, Mark Messier, Victor Cruz, Mookie Wilson, Ryan Callahan, Don Larsen, Joe Morris, Otis Anderson, John Starks, and many more as they visited and signed memorabilia that would be auctioned to raise needed funds.
"It was an honor cooking for a World Series Champion (Rivera), a Super Bowl Champ,?and a Stanley Cup Champion all in one day!" says Meat House chef Joseph?Brakatselos.
WASHINGTON, D.C. - The House of Representatives may introduce its version of the Violence Against Women Act this week, as Congress attempts to reauthorize an 18-year-old law designed to strengthen legal protections against victims of domestic violence.
But prospects for the attempt to combine House Republican proposals for the law with the version passed by the Senate in April remain unclear as the year-end deadline draws near.
The two bills are relatively similar, with the exception of three additions favored on the Senate side: expanded protections for the gay community, undocumented immigrants, and Native American women. Today Democratic women in the Senate said a House bill would be dead on arrival without those aspects.
"A bill like that is an absolute non starter in the Senate," said Sen. Patty Murray of Washington, pointing out their version passed with a strongly bipartisan 68-31 votes last spring.
Murray and her colleagues appealed to female members of the House GOP at a press conference this morning. Sen. Kay Hagan of North Carolina was more blunt in her remarks.
"A 911 operator doesn't take that call and ask, 'Who is that on this on the other end of the line? Are you an immigrant? Are you gay? Are you on an Indian reservation? They respond to that call like everyone expects them to do," she said.
Under current law, undocumented immigrants who are victims of domestic violence can be given a temporary visa, partly as incentive to come forward to authorities. The House bill denies a Democratic attempt to raise the cap on the number of visas available for the program, and removes a standing ability for that victim to apply for permanent residency after three years.
Meanwhile, Native American women on Indian reservations are currently exempt from the law due to jurisdictional boundaries between state, federal, and tribal governments. The Senate bill would allow non-native perpetrators of abuse on those women to be tried in tribal courts if living on tribal land.
According to the U.S. Census, 50 percent of Native American married women are in relationships with non-Indian men.
Opponents of the Senate bill also cite duplicate programs and failure to expand protections against potential fraud as reason for concern, in addition to expanding costs. The Congressional Budget Office reports the Violence Against Women Act costs taxpayers $660 million annually to support.
Negotiations are being spearheaded by House Majority Leader Eric Cantor and Vice President Biden, who was involved with the original bill's introduction in 1994, when he was a senator. But while most of the political rhetoric in Washington lately has been directed at the "fiscal cliff," both parties have been relatively silent on this matter - a possible testament to how serious each side is about reaching an agreement.
Last week, 10 House Republicans signed a letter to that chamber's leadership urging passage of a bill "similar to that which has already passed the Senate." The letter was sponsored by Democratic Rep. Gwen Moore of Wisconsin, and was signed overwhelmingly by members of that party.
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If you are ready to list your home for sale you want to make sure it is in top condition.?Spending a little time on regular maintenance will help ensure it is one of the best homes for sale in Denver.
There are several?regular maintenance tasks that you should undertake before winter hits, including:
Reversing ceiling fans
Check to see if your ceiling fans have a reverse mode. Simply switching the direction of the fan?s blades will produce an updraft and will push heat down from a room?s ceiling.
Turning off and covering exterior faucets
Make sure that each exterior faucet is turned off.?You should also invest a few dollars in faucet covers that provide insulation from cold winter winds and snow.
Cleaning gutters
Choose a clear, dry day to inspect and clean out your home?s gutters.?Clogged gutters may back up with water and can damage your home?s siding, trim, and roof.
Inspecting the roof
While you are on the ladder cleaning out your gutters it is also a good idea to take a look at the roof.?Use binoculars to inspect for loose or damaged shingles and replace and repair any areas in need of attention.
If you would like additional information on homes for sale in Denver contact the real estate experts with Preferred Properties.?We are committed to the real estate needs of the Denver area and the residents that call it home.
Though lacking the social import of gay marriage or marijuana legalization, the issue of mobile device use on airplanes is heating up again. Now government agencies appear to be bickering about it. The FCC sent the FAA a letter telling it to get off the lavatory and revise the rules. What most people don't realize is the FAA doesn't make the rules, and it was the FCC that banned cell phone use in particular.
In the meantime, both casual and frequent flyers are frothing over whether passengers should be permitted to use their devices during takeoff and landing. Arguments on both sides range from sensible to preposterous. The science is murky and the research takes too long. And while the FAA is profoundly irresolute about whether or not there is any real danger in using personal devices on a plane, the agency is probably not sufficiently motivated to create change.
Continue reading Editorial: Devices on planes -- either enforce the rules or change them
Filed under: Misc, Tablets, Transportation, Wireless, Apple
Source: http://www.engadget.com/2012/12/11/devices-on-planes/
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Public release date: 6-Dec-2012
Share ] Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
SAN FRANCISCO, CADecember 6, 2012Scientists at the Gladstone Institutes have identified a novel mechanism by which a type of low-carb, low-calorie dietcalled a "ketogenic diet"could delay the effects of aging. This fundamental discovery reveals how such a diet could slow the aging process and may one day allow scientists to better treat or prevent age-related diseases, including heart disease, Alzheimer's disease and many forms of cancer.
As the aging population continues to grow, age-related illnesses have become increasingly common. Already in the United States, nearly one in six people are over the age of 65. Heart disease continues to be the nation's number one killer, with cancer and Alzheimer's close behind. Such diseases place tremendous strain on patients, families and our healthcare system. But today, researchers in the laboratory of Gladstone Senior Investigator Eric Verdin, MD, have identified the role that a chemical compound in the human body plays in the aging processand which may be key to new therapies for treating or preventing a variety of age-related diseases.
In the latest issue of the journal Science, available online today, Dr. Verdin and his team examined the role of the compound ?-hydroxybutyrate (?OHB), a so-called "ketone body" that is produced during a prolonged low-calorie or ketogenic diet. While ketone bodies such as ?OHB can be toxic when present at very high concentrations in people with diseases such as Type I diabetes, Dr. Verdin and colleagues found that at lower concentrations, ?OHB helps protect cells from "oxidative stress"which occurs as certain molecules build to toxic levels in the body and contributes to the aging process.
"Over the years, studies have found that restricting calories slows aging and increases longevityhowever the mechanism of this effect has remained elusive" Dr. Verdin said. Dr. Verdin, the paper's senior author, directs the Center for HIV & Aging at Gladstone and is also a professor at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we find that ?OHBthe body's major source of energy during exercise or fastingblocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from aging."
Oxidative stress occurs as cells use oxygen to produce energy, but this activity also releases other potentially toxic molecules, known as free radicals. As cells age, they become less effective in clearing these free radicalsleading to cell damage, oxidative stress and the effects of aging.
However, Dr. Verdin and his team found that ?OHB might actually help delay this process. In a series of laboratory experimentsfirst in human cells in a dish and then in tissues taken from micethe team monitored the biochemical changes that occur when ?OHB is administered during a chronic calorie-restricted diet. The researchers found that calorie restriction spurs ?OHB production, which blocked the activity of a class of enzymes called histone deacetylases, or HDACs.
Normally HDACs keep a pair of genes, called Foxo3a and Mt2, switched off. But increased levels of ?OHB block the HDACs from doing so, which by default activates the two genes. Once activated, these genes kick-start a process that helps cells resist oxidative stress. This discovery not only identifies a novel signaling role for ?OHB, but it could also represent a way to slow the detrimental effects of aging in all cells of the body.
"This breakthrough also greatly advances our understanding of the underlying mechanism behind HDACs, which had already been known to be involved in aging and neurological disease," said Gladstone Investigator Katerina Akassoglou, PhD, an expert in neurological diseases and one of the paper's co-authors. "The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injurydiseases that afflict millions and for which there are few treatment options."
"Identifying ?OHB as a link between caloric restriction and protection from oxidative stress opens up a variety of new avenues to researchers for combating disease," said Tadahiro Shimazu, a Gladstone postdoctoral fellow and the paper's lead author. "In the future, we will continue to explore the role of ?OHBespecially how it affects the body's other organs, such as the heart or brainto confirm whether the compound's protective effects can be applied throughout the body."
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Matthew Hirschey, PhD; John Newman, MD, PhD; Wenjuan He, PhD; Kotaro Shirakawa, PhD; Natacha Le Moan, PhD; Carrie Grueter, PhD; Hyungwook Lim, PhD; Laura Saunders, PhD; Robert V. Farese, Jr., MD; and Katerina Akassoglou, PhD, also participated in this research at Gladstone. This research was supported by the Gladstone Institutes.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
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Public release date: 6-Dec-2012 Share ] Contact: Anne Holden
anne.holden@gladstone.ucsf.edu
415-734-2534
Gladstone Institutes
SAN FRANCISCO, CADecember 6, 2012Scientists at the Gladstone Institutes have identified a novel mechanism by which a type of low-carb, low-calorie dietcalled a "ketogenic diet"could delay the effects of aging. This fundamental discovery reveals how such a diet could slow the aging process and may one day allow scientists to better treat or prevent age-related diseases, including heart disease, Alzheimer's disease and many forms of cancer.
As the aging population continues to grow, age-related illnesses have become increasingly common. Already in the United States, nearly one in six people are over the age of 65. Heart disease continues to be the nation's number one killer, with cancer and Alzheimer's close behind. Such diseases place tremendous strain on patients, families and our healthcare system. But today, researchers in the laboratory of Gladstone Senior Investigator Eric Verdin, MD, have identified the role that a chemical compound in the human body plays in the aging processand which may be key to new therapies for treating or preventing a variety of age-related diseases.
In the latest issue of the journal Science, available online today, Dr. Verdin and his team examined the role of the compound ?-hydroxybutyrate (?OHB), a so-called "ketone body" that is produced during a prolonged low-calorie or ketogenic diet. While ketone bodies such as ?OHB can be toxic when present at very high concentrations in people with diseases such as Type I diabetes, Dr. Verdin and colleagues found that at lower concentrations, ?OHB helps protect cells from "oxidative stress"which occurs as certain molecules build to toxic levels in the body and contributes to the aging process.
"Over the years, studies have found that restricting calories slows aging and increases longevityhowever the mechanism of this effect has remained elusive" Dr. Verdin said. Dr. Verdin, the paper's senior author, directs the Center for HIV & Aging at Gladstone and is also a professor at the University of California, San Francisco, with which Gladstone is affiliated. "Here, we find that ?OHBthe body's major source of energy during exercise or fastingblocks a class of enzymes that would otherwise promote oxidative stress, thus protecting cells from aging."
Oxidative stress occurs as cells use oxygen to produce energy, but this activity also releases other potentially toxic molecules, known as free radicals. As cells age, they become less effective in clearing these free radicalsleading to cell damage, oxidative stress and the effects of aging.
However, Dr. Verdin and his team found that ?OHB might actually help delay this process. In a series of laboratory experimentsfirst in human cells in a dish and then in tissues taken from micethe team monitored the biochemical changes that occur when ?OHB is administered during a chronic calorie-restricted diet. The researchers found that calorie restriction spurs ?OHB production, which blocked the activity of a class of enzymes called histone deacetylases, or HDACs.
Normally HDACs keep a pair of genes, called Foxo3a and Mt2, switched off. But increased levels of ?OHB block the HDACs from doing so, which by default activates the two genes. Once activated, these genes kick-start a process that helps cells resist oxidative stress. This discovery not only identifies a novel signaling role for ?OHB, but it could also represent a way to slow the detrimental effects of aging in all cells of the body.
"This breakthrough also greatly advances our understanding of the underlying mechanism behind HDACs, which had already been known to be involved in aging and neurological disease," said Gladstone Investigator Katerina Akassoglou, PhD, an expert in neurological diseases and one of the paper's co-authors. "The findings could be relevant for a wide range of neurological conditions, such as Alzheimer's, Parkinson's, autism and traumatic brain injurydiseases that afflict millions and for which there are few treatment options."
"Identifying ?OHB as a link between caloric restriction and protection from oxidative stress opens up a variety of new avenues to researchers for combating disease," said Tadahiro Shimazu, a Gladstone postdoctoral fellow and the paper's lead author. "In the future, we will continue to explore the role of ?OHBespecially how it affects the body's other organs, such as the heart or brainto confirm whether the compound's protective effects can be applied throughout the body."
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Matthew Hirschey, PhD; John Newman, MD, PhD; Wenjuan He, PhD; Kotaro Shirakawa, PhD; Natacha Le Moan, PhD; Carrie Grueter, PhD; Hyungwook Lim, PhD; Laura Saunders, PhD; Robert V. Farese, Jr., MD; and Katerina Akassoglou, PhD, also participated in this research at Gladstone. This research was supported by the Gladstone Institutes.
About the Gladstone Institutes
Gladstone is an independent and nonprofit biomedical-research organization dedicated to accelerating the pace of scientific discovery and innovation to prevent, treat and cure cardiovascular, viral and neurological diseases. Gladstone is affiliated with the University of California, San Francisco.
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Source: http://www.eurekalert.org/pub_releases/2012-12/gi-gsd120512.php
