An Obama initiative seeks to channel a torrent of gene information into treatments for cancer, other diseases.

President Barack Obama is proposing to spend $215 million on a precision medicine initiative the centerpiece of which will be a national study involving the health records and DNA of one million volunteers, administration officials said yesterday.

Precision medicine refers to treatments tailored to a persons genetic profile, an idea already transforming how doctors fight cancer and some rare diseases.

The Obama plan, including support for studies of cancer and rare disease, is part of a shift away from one-size-fits-all medicine, Jo Handelsman, associate director for the White House Office of Science and Technology Policy, said in a briefing yesterday. She called precision medicine a game changer that holds the potential to revolutionize how we approach health in this country and around the world.

The White House said the largest part of the money, $130 million, would go to the National Institutes of Health in order to create a population-scale study of how peoples genes, environment, and lifestyle affect their health.

According to Francis Collins, director of the National Institutes of Health, the study will recruit new volunteers as well as merging data from several large studies already under way. Details still need to be sorted out, said Collins, but the study could eventually involve completely decoding the genomes of hundreds of thousands of people.

Officials indicated that patients might have more access to data generated about them than is usually the case in research studies. That is partly because scientists will need the ability to re-contact them, should their genes prove interesting.

We arent just talking about research but also about patients access to their own data, so they can participate fully in decisions about their health that affect them, said John Holdren, director of the White House Office of Science and Technology Policy.

The Obama initiative, which the president first announced during his State of the Union address, also allocates $70 million for DNA-driven research on cancer and another $10 million for the U.S. Food and Drug Administration, which has struggled to regulate genome tests.

Collins said the U.S. is not seeking to create a single bio-bank. Instead, the project would look to combine data from among what he called more than 200 large American health studies that are ongoing and together involve at least two million people. Fortunately, we dont have to start from scratch, he said. The challenge of this initiative is to link those together. Its more a distributed approach than centralized.

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U.S. to Develop DNA Study of One Million People

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UT Southwestern Medical Center scientists have identified a strong link between the most aggressive type of breast cancer and a gene that regulates the body's natural cellular recycling process, called autophagy.

Based on analysis of two large breast cancer databases, reduced activity of an autophagy gene, beclin 1, was related to both a higher incidence of triple-negative breast cancer and a poorer prognosis for breast cancer patients.

The study, published in the online journal EBioMedicine, is the first to document a correlation between beclin 1 and triple-negative human breast cancer and validates research in mouse models.

"We have potentially identified a new pathway to be targeted in the most aggressive, difficult-to-treat form of breast cancer," said Dr. Beth Levine, Director of the Center for Autophagy Research and a Howard Hughes Medical Institute Investigator at UT Southwestern. "These data suggest that decreased beclin 1 activity contributes to breast cancer and poor survival outcomes. As a result, therapies that increase beclin 1 activity in breast cancer may be beneficial."

Triple-negative breast cancer -- which accounts for 10 to 20 percent of breast cancer -- is called such because the cancer's cells lack estrogen and progesterone receptors and also do not have an excess of the human growth factor receptor 2 (HER2) protein on their surfaces. Chemotherapy, the standard treatment, has been limited in its effectiveness against triple-negative breast cancer.

"With low beclin 1 expression, you have up to a 35-fold higher risk of having triple-negative breast cancer. That's really strong," said Dr. Levine, who holds the Charles Cameron Sprague Distinguished Chair in Biomedical Science and is co-senior author of the study with Dr. Yang Xie, Associate Professor of Clinical Science.

UT Southwestern researchers analyzed 3,057 breast cancer cases for levels of expression of beclin 1 and BRCA1, a nearby gene that is associated with inherited breast cancer. The data came from The Cancer Genome Project in the United States (1,067 cases) and the Molecular Taxonomy of Breast Cancer International Symposium in the United Kingdom and Canada (1,992 cases).

"We know that about 35 percent of all breast cancers are missing copies of both the beclin 1 and BRCA1 genes," said Dr. Levine. "To find out which of the two genes is important, we looked at the levels of expressions of both genes and how they related to different clinical features of breast cancer. Strong associations were seen between low expression of beclin 1, but not BRCA1, and adverse clinical features."

Along with the 35-fold higher risk of having triple-negative breast cancer, the findings showed low levels of beclin 1 activity also correlated with worse outcomes.

"Patients with breast cancer and low beclin 1 expression had a 67 percent increase in the risk of dying from breast cancer compared with patients who had higher levels of beclin 1 expression," Dr. Xie said.

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To retain and attract top talent, a quarter of UK businesses would extend health screening into genetic testing but fear of legal repercussions is an inhibiting factor for 76% of employers

With the price of full DNA testing plummeting, and in anticipation of personalised medicines fine-tuned to a patient's genetic make-up, one in four (24%) UK businesses say that they are likely to extend health screening into genetic testing as they strive to retain and attract top talent, a new survey has found.

UK businesses could soon offer employees a complete readout of their genetic blueprint, and hence unprecedented insight into their current and future health, but, amidst all the excitement, Baroness Helena Kennedy, QC, Vice President of the Patients Association and former Chair of the Human Genetics Committee, urges businesses to consider the wider implications, suggesting that genetic screening of employees may be more of a Pandoras box than a panacea.

More than 600 UK business leaders were questioned for the Astellas Innovation DebateTM 2015, which on Thursday 29th January brings together a panel of world-renowned experts at The Royal Institution of Great Britain to discuss the implications of the revolutions in DNA and data for our health.1

Currently, one in four (24%) business leaders say they would offer full genetic screening to their employees though this rises to nearly a third (29%) in the IT and banking sectors, where talent often seems in short supply. But most employers (76%) the fear of legal repercussions is an inhibiting factor.

Of employers who said that their business would be unlikely to offer genetic screening to employees, 43% said they might reconsider their view in the future if better legislation were introduced to protect the rights of employers (19%) and employees (24%). 16% said they would re-consider their view if the results of genetic testing could serve to reduce the cost of key person insurance, while a further 16% said that businesses would need access to advice on dealing with employees found to be at higher genetic risk of developing serious illness. Only 5% said they might choose to offer genetic screening if their business could access genetic data from test results.

European legislation prohibits businesses from gaining access to their employees genetic data, and most businesses (72%) support this principle. Despite that, one in five bosses (22%) admitted that an employee who revealed his/her greater genetic risk of serious illness would consequently also run a greater risk of redundancy and become less eligible for promotion.

Baroness Helena Kennedy, QC, a panellist at the Astellas Innovation Debate Vice President of the Patients Association, and former Chair of the Human Genetics Commission, where she successfully pushed for a moratorium on access to genetic records for insurance companies and persuaded the Government to make it a criminal offence to test DNA without an individuals consent, commented:

Of course its a testament to mankinds ingenuity that genetics and technology are combining to bring the prospect of personalised medicine much closer. But knowing the facts about our genes can also bring challenges. For example, our genetic information could be misused by insurers, who could over-interpret the information in our genes, wrongly suspect we are susceptible to some disease, and so not provide us with the kind of insurance we need. Similarly, if an employee shared some genetic information with his or her boss that indicated a higher risk of, say, cancer or a neurological disease, as this survey shows the employee would be at higher risk of discrimination in the workplace in the form of redundancy or being passed over for promotion. This in turn leaves the employer vulnerable to accusations of discrimination. And then, on a personal level, employees might well need professional support if they become distressed at the prospect of a disease that they might or might not develop.

Some US technology companies are offering employees DNA screening to identify the risk of cancers, and holding out the promise of personalised treatment based on their genetic make-up should they need it. However, I would urge UK businesses not to follow suit certainly not without thinking very carefully about the wider implications to them and their employees. It is not just a matter of potential discrimination and lawsuits, but also of the health benefits to those being tested. Of course, we all recognise the importance of screening people with a family history of certain diseases and rare genetic disorders as the 100,000 Genomes Project is currently doing but there is little benefit to widespread genetic testing if it cant tell you when or even if you will develop the disease.

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The Obama administration is proposing to create a large database of patient information, including genetic profiles and medical histories, to further research into precision medicine, which aims to create customized treatments based on a patients genetic makeup and lifestyle choices.

Precision, or personalized, medicine works much the same way that an eyeglass prescription or a blood transfusion is prescribed, based on a patient's exam results or blood type, and proponents believe this line of thinking may be extended to many more areas of medicine.

Jo Handelsman, associate director for science at the White House Office of Science and Technology, has called the $215 million budget allocation for the Precision Medicine Initiative in Obamas proposed 2016 budget a move away from the one-size-fits-all approach to medicine.

Obama's proposal grants $130 million to the National Institutes of Health to launch a national long-term study that will collect biological samples, genetic profiles and electronic health records from at least a million Americans.

Researchers may use an app to track the calorie consumption or environmental health impacts of participants through their smartphones and the database could include everything from their laboratory test results to MRI scans. Patient data will be anonymized and participation is strictly voluntary, the administration says. The system is meant to serve as a reservoir of information that researchers can tap while investigating the nuances of a particular disease in individual patients, or trying to identify genetic trends across treatment groups.

The administration, with its messy record of privacy violations committed in the name of national security, will also grant $5 million to the Office of the National Coordinator for Health Information Technology to build a data system that it says will protect the identities of patients whose information is included in the database. The National Institutes of Health will also host a forum in mid-February to discuss the challenges of creating a national research group to populate the database. Much of the patient information may be pulled from existing studies, according to scientists familiar with the project who spoke on background to Science magazine.

Obama gave researchers a glimpse into his zeal for precision medicine during the 2015 State of the Union address, but he clarified the details Friday.I want the country that eliminated polio and mapped the human genome to lead a new era of medicine -- one that delivers the right treatment at the right time, he said in his address.

The Cystic Fibrosis Foundation has long taken this approach to develop customized drugs for small groups of patients who share the same genetic mutation for the disease. The organization worked with Vertex Pharmaceuticals to create a drug called Kalydeco, which treats a mutation present in only4 percent of patients with cystic fibrosis according to a 2012 study in the American Journal of Respiratory and Critical Care Medicine. This focus on tailor-made medicine has nearly doubled the median life span of patients from 20 years to 40 years.

This research will dramatically advance our knowledge of diseases, how they originated and how we may prevent or treat them, Francis Collins, director of the National Institutes of Health, told the Washington Post.

Looking ahead, the administration is anxious to try to apply the same principles that have worked for cystic fibrosis to cancer. Obamas proposal requests $70 million for the National Cancer Institute to study the genetic underpinnings of several types of the disease, reports the New York Times.

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The United States has proposed analysing genetic information from more than 1 million American volunteers as part of a new initiative to understand human disease and develop medicines targeted to an individual's genetic make-up.

At the heart of the "precision medicine" initiative, announced todayby President Barack Obama, is the creation of a pool of people - healthy and ill, men and women, old and young - who would be studied to learn how genetic variants affect health and disease.

Officials hope genetic data from several hundred thousand participants in ongoing genetic studies would be used and other volunteers recruited to reach the 1 million total.

"Precision medicine gives us one of the greatest opportunities for new medical breakthroughs we've ever seen," Obama said, promising that it would "lay a foundation for a new era of life-saving discoveries."

The near-term goal is to create more and better treatments for cancer, Dr. Francis Collins, director of the National Institutes of Health (NIH), told reporters on a conference call on Thursday.

Longer term, he said, the project would provide information on how to individualize treatment for a range of diseases.

The initial focus on cancer, he said, reflects the lethality of the disease and the significant advances against cancer that precision medicine has already made, though more work is needed.

The president proposed $215 million in his 2016 budget for the initiative. Of that, $130 million would go to the NIH to fund the research cohort and $70 million to NIH's National Cancer Institute to intensify efforts to identify molecular drivers of cancer and apply that knowledge to drug development.

A further $10 million would go to the Food and Drug Administration to develop databases on which to build an appropriate regulatory structure; $5 million would go to the Office of the National Coordinator for Health Information Technology to develop privacy standards and ensure the secure exchange of data.

The effort may raise alarm bells for privacy rights advocates who have questioned the government's ability to guarantee that DNA information is kept anonymous.

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Speaking at the White House on Jan. 30, President Obama urged support for a section in his budget proposal that would fund research in the field of "precision" or "personal" medicine. Here are highlights from that speech.

President Obama, in announcing an ambitious plan on Friday to invest hundreds of millions of dollars in cutting-edge biomedical research for treatments tailored to the genetic makeup of individual patients, said the effort would lay the foundation for a new generation of lifesaving discoveries.

In recent years, targeted therapies have led to more effective treatments for various cancers and other diseases, such as cystic fibrosis. The Food and Drug Administration has approved a growing number of specialized drugs for patients with specific genetic mutations, and the biotech industry has many more drugs in development.

The trend has benefited from sharp declines in the cost of genome sequencing. Decoding one persons genome, which used to cost hundreds of millions of dollars, costs about $1,000. Storing massive amounts of data is cheaper than ever, and the world is increasingly connected by mobile technologies and electronic medical records.

Lawmakers from both parties have embraced the broad idea of speeding up medical innovation, even if the details about how best to do that remain unresolved.

The really good news this is how you know that the moment is right is theres bipartisan support for the idea here in Washington, Obama said in the East Room on Friday morning, drawing a laugh from the crowd of renowned researchers, rare disease patients and officials from the biotech industry. Which makes me very happy.

Obama said he hopes to tap that bipartisan support and ask Congress for a $215 million for research on precision medicine. The request will be part of his annual budget scheduled for release Monday.

Still, for all its promise, the potentially staggering cost of some of the targeted drugs that have this kind of research has raised concerns.

Kalydeco, a drug approved in 2012 and highlighted by Obama on Friday, has done wonders for about 4 percent of cystic fibrosis patients with a specific genetic mutation. But it carries a price tag of about $300,000 a year.

We want to be sure that when these drugs come to market, they arent priced at a level people cant afford, said John Rother, president of the National Coalition on Health Care, which represents insurers, employers and consumer and religious groups, among others. Thats not the kind of world we want to live in.

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Friday, January 30 17:16:45

The United States has proposed analyzing genetic information from more than 1 million American volunteers as part of a new initiative to understand human disease and develop medicines targeted to an individual's genetic make-up.

At the heart of the "precision medicine" initiative, announced on Friday by President Barack Obama, is the creation of a pool of people - healthy and ill, men and women, old and young - who would be studied to learn how genetic variants affect health and disease.

Officials hope genetic data from several hundred thousand participants in ongoing genetic studies would be used and other volunteers recruited to reach the 1 million total.

"Precision medicine gives us one of the greatest opportunities for new medical breakthroughs we've ever seen," Obama said, promising that it would "lay a foundation for a new era of life-saving discoveries."

The near-term goal is to create more and better treatments for cancer, Dr. Francis Collins, director of the National Institutes of Health (NIH), told reporters on a conference call on Thursday. Longer term, he said, the project would provide information on how to individualize treatment for a range of diseases.

The initial focus on cancer, he said, reflects the lethality of the disease and the significant advances against cancer that precision medicine has already made, though more work is needed.

The president proposed $215 million in his 2016 budget for the initiative. Of that, $130 million would go to the NIH to fund the research cohort and $70 million to NIH's National Cancer Institute to intensify efforts to identify molecular drivers of cancer and apply that knowledge to drug development.

A further $10 million would go to the Food and Drug Administration to develop databases on which to build an appropriate regulatory structure; $5 million would go to the Office of the National Coordinator for Health Information Technology to develop privacy standards and ensure the secure exchange of data.

The effort may raise alarm bells for privacy rights advocates who have questioned the government's ability to guarantee that DNA information is kept anonymous.

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US want to analyse DNA of 1m people

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InterAksyon.com The online news portal of TV5

WASHINGTON - The United States has proposed analyzing genetic information from more than 1 million American volunteers as part of a new initiative to understand human disease and develop medicines targeted to an individual's genetic make-up.

At the heart of the "precision medicine" initiative, announced on Friday by PresidentBarackObama, is the creation of a pool of people - healthy and ill, men and women, old and young - who would be studied to learn how genetic variants affect health and disease.

Officials hope genetic data from several hundred thousand participants in ongoing genetic studies would be used and other volunteers recruited to reach the 1 million total.

"Precision medicine gives us one of the greatest opportunities for new medical breakthroughs we've ever seen," Obama said, promising that it would "lay a foundation for a new era of life-saving discoveries."

The near-term goal is to create more and better treatments for cancer, Dr. Francis Collins, director of the National Institutes of Health (NIH), told reporters on a conference call on Thursday. Longer term, he said, the project would provide information on how to individualize treatment for a range of diseases.

The initial focus on cancer, he said, reflects the lethality of the disease and the significant advances against cancer that precision medicine has already made, though more work is needed.

The president proposed $215 million in his 2016 budget for the initiative. Of that, $130 million would go to the NIH to fund the research cohort and $70 million to NIH's National Cancer Institute to intensify efforts to identify molecular drivers of cancer and apply that knowledge to drug development.

A further $10 million would go to the Food and Drug Administration to develop databases on which to build an appropriate regulatory structure; $5 million would go to the Office of the National Coordinator for Health Information Technology to develop privacy standards and ensure the secure exchange of data.

The effort may raise alarm bells for privacy rights advocates who have questioned the government's ability to guarantee that DNA information is kept anonymous.

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President Obama on Friday rolled out a proposal to invest $215 million this year in an initiative to advance "precision medicine," an approach to disease prevention and treatment that moves beyond a "one-size-fits" all approach.

Precision medicine "gives us one of the greatest opportunities for new medical breakthroughs that we have ever seen," Mr. Obama said from the East Room of the White House.

"Doctors have always recognized that every patient is unique," he continued, noting that doctors that can match a blood transfusion to a blood type.

"What if matching a cancer cure to our genetic code was just as easy?" the president asked. "That's the promise of precision medicine, delivering the right treatments at the right time, every time, to the right person."

Precision medicine takes into account people's genes, environments and lifestyles, giving clinicians tools to better understand the mechanisms underlying certain diseases and conditions -- and which treatments to use. Already, it's used for a small but growing number of patients. For instance, doctors can use genetic testing to determine whether an HIV patient will be helped by a certain antiviral drug.

"What's so exciting is we have the possibility of leading a new era of medicine," Mr. Obama said.

"We shouldn't just celebrate innovation, we have to invest in innovation... and make sure that we're channeling it in ways that are most productive," he continued, noting how the Polio vaccine was distributed widely with the help of Congress.

Mr. Obama said the time is right to invest in precision medicine because of the advances in technology and medicine, as well as the bipartisan political support for it.

"This is how you know the moment is right, is there's bipartisan support for the idea here in Washington," he said.

Specifically, Mr. Obama's budget will include a proposal to give the National Institutes of Health (NIH) $130 million for the development of a voluntary national research cohort of at least a million volunteers. The proposal would give $70 million to the National Cancer Institute (part of NIH) to scale up efforts to identify genomic drivers in cancer. Another $10 million would go to the Food and Drug Administration to develop high-quality databases for the reach, while the Office of the National Coordinator for Health Information Technology would get $5 million to develop privacy and security standards for the research.

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Bio 10.2.2 - Laws of Genetics

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Best Outdoor Strain 2014 - DNA Genetics - Holy Grail Kush - Herbies Awards
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Mephisto Genetics Chem City Blues Autoflower under Grownorthern Holographic Series 1,
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Fertility Center Applied Genetics Sarasota Incredible Five Star Review
http://GeneticsAndFertility.com 941-342-1568 Fertility Center Applied Genetics Sarasota reviews New Review We are so thankful that we have picked Dr. Pabon! I #39;m now in my...

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Gene Therapy Pioneer Ted Friedman Awarded Japan Prize
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Shares of Spark Therapeutics, the Philadelphia gene therapy developer backed by Childrens Hospital of Philadelphia, zoomed as high as $45 a share after trading opened at $23 in its initial public stock offering (IPO) led by JPMorgan and Credit Suisse.

The company said it grossed $161 milllion, before payments to brokers, by selling 7 million shares (ticker symbol: ONCE) to investors on the Nasdaq stock market at $23/share. But a surge of investor interest in the company boosted Spark's total value (including shares still held by earlier investors before it went public) to nearly $1 billion, and increased the value of 4.9 million shares owned by CHOP, according to previous federal securities filings, to as much as $220 million.

Chief executive Jeff Marrazzo is another major beneficiary: he owns 380,000 shares, now worth around $16 million, according to federal securities records. Spark's statement on the IPO here.More on Spark's structure, investors, founders and early products in my Philadelphia Inquirer colleague David Sell's Jan. 2 story here.Spark investor prospectus with more detail on what they're going to do with the money here.

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Denver Regenerative Medicine - What is regenerative medicine?
Dr. Joel Cherdack of Denver Regenerative Medicine explains what regenerative medicine is. He and the hosts discuss the benefits of both PRP (platelet rich plasma) and Stem Cell Therapy.

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TORONTO - Two Canadian research centres are gearing up for a clinical trial to determine if a type of stem cell can help alleviate the symptoms of multiple sclerosis.

Researchers at the Ottawa Hospital and Winnipeg's Health Sciences Centre will each recruit 20 MS patients for the trial that will test whether mesenchymal stem cells can reduce inflammation and even help repair damage already caused by the disease.

MS is thought to be an autoimmune disease that creates inflammation in the central nervous system, resulting in injury to myelin, the protective sheath that covers nerves. This damage can create a host of symptoms, leading to varying degrees of physical disability and cognitive impairment.

Mesenchymal stem cells, which are found in bone marrow, fat, skin tissue and umbilical cord blood, have the ability to modify the immune system and reduce inflammation, said neurologist Dr. Mark Freedman of the Ottawa Hospital Research Institute, who is leading the clinical trial.

Freedman said researchers want to determine if these stem cells can demonstrate anti-inflammatory properties in patients with MS.

"But that's not why we're doing it," he said of the study, called MESCAMS ("MEsenchymal Stem cell therapy for CAnadian MS patients"). "We have lots of drugs that can control inflammation in multiple sclerosis that's what all the new medicines do."

"The ultimate hope is that we will be able to exploit some of their other very important biological properties, which is to promote repair."

The two research centres are ready to begin enrolling patients for the trial, which has specific acceptance criteria. While most of those accepted will likely have the relapsing-remitting form of the disease, Freedman said some people with more severe primary- or secondary-progressive MS may also be eligible if they fit the criteria.

The study protocol can be accessed at http://www.clinicaltrials.gov/show/NCT02239393. It will later be posted on the website of the MS Society of Canada, which along with the Multiple Sclerosis Scientific Research Foundation has provided a $4.2-million grant for the study.

To conduct the trial, half the patients will be randomly assigned to receive their own mesenchymal stem cells within weeks of them being extracted from the bone marrow and grown in the lab; the remainder of the participants will instead be infused with a mock stem-cell solution, and won't receive their actual stem cells for about six months. The two groups will then be compared.

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10 hours ago Researchers at Cold Spring Harbor Laboratory have uncovered a remarkable, new proofreading mechanism. In general, enzymatic machines are responsible for weeding out and correcting errors. But a team of scientists has found that the CCA-adding enzyme (shown here in blue, green, and pink) doesn't edit at all. Instead, the RNA (in orange) has a built-in mechanism that allows it to proofread itself. Credit: L. Joshua-Tor, Cold Spring Harbor Laboratory

Building a protein is a lot like a game of telephone: information is passed along from one messenger to another, creating the potential for errors every step of the way. There are separate, specialized enzymatic machines that proofread at each step, ensuring that the instructions encoded in our DNA are faithfully translated into proteins. Scientists at Cold Spring Harbor Laboratory (CSHL) have uncovered a new quality control mechanism along this path, but in a remarkable role reversal, the proofreading isn't done by an enzyme. Instead, one of the messengers itself has a built-in mechanism to prevent errors along the way.

The building blocks for proteins are carried by molecules known as transfer RNAs (tRNAs). tRNAs work with other cellular machinery to ensure that the building blocks - amino acids - are arranged in the proper order. But before a building block can be loaded onto a tRNA molecule, a three-part chemical sequence that scientists call "CCA" must be added to the tRNA. The letters are added by an appropriately named machine, the CCA-adding enzyme, and they mark the tRNA as a fully functional molecule.

If a tRNA is mutated, the CCA-adding enzyme duplicates its message. The letters now read "CCACCA," signaling that the tRNA is flawed. The cell rapidly degrades the aberrant tRNA, preventing the flawed message from propagating.

But how does the CCA-adding enzyme distinguish between normal and mutant tRNAs?

CSHL Professor and Howard Hughes Medical Institute Investigator Leemor Joshua-Tor led a team of researchers to investigate how the CCA-adding enzyme makes this distinction. "We used X-ray crystallography - a type of molecular photography - to observe the enzyme at work, and we were surprised to find that the enzyme doesn't discriminate at all," explains Joshua-Tor. "In fact, it is the RNA that is responsible for proofreading itself."

The team used two tRNA-like molecules, called noncoding RNAs, to study the error-correcting mechanism. In previous work, Jeremy Wilusz, PhD, a former CSHL Watson School of Biological Sciences graduate student and an author on this current publication, found a noncoding RNA that is modified with a single CCA group, making it both stable and abundant. Another RNA used in the current study is normally present at negligible levels in cells, and Wilusz and CSHL Professor David Spector found that it is modified with a CCACCA sequence and is rapidly degraded. The difference between the two noncoding RNAs is a simple mutation, and the question the team addressed is how the presence of the mutation affects the addition of "CCA" sequences.

In work published online today in Cell, the team describes a series of molecular photographs of the CCA-adding enzyme bound to the noncoding RNAs. "The CCA-adding enzyme uses a screw-like motion to add each letter of the CCA group to the end of the RNA," says Claus Kuhn, PhD, lead author on the paper. "Under normal circumstances, after the addition of the final letter A, the enzyme tries to 'turn' the molecule again, but can't." That increased pressure forces the RNA to pop out of its union with the enzyme - with only a single CCA group attached.

But when an RNA is mutated, the researchers found, the structure becomes more flexible. After a single CCA addition, the mutation allows the RNA to buckle under increased pressure. "That bulge allows the enzyme to add an additional round of "CCA" letters, and only then does the RNA pop out," says Joshua-Tor.

This is a very unique proofreading mechanism, according to Joshua-Tor. "For the enzyme, there is no difference between the two RNAs - it adds CCA in this screw-like motion regardless of what the sequence is. So it is a mutation in the RNA itself that prevent future errors," ensuring that proteins are made correctly.

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Rev Diabet Stud. 2009 Winter; 6(4): 260270.

1Tissue Engineering and Banking Laboratory, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India

2Division of Animal Sciences, Agharkar Research Institute, Agarkar Road, Pune, MH 411004, India

3Stem Cells and Diabetes Section, National Center for Cell Science, Ganeshkhind Road, Pune MH 411007, India

4Stempeutics Research Pvt. Ltd., 9th Floor, Manipal Hospital, HAL Airport Road, Bangalore 560017, India

Received October 2, 2009; Revised December 5, 2009; Accepted December 11, 2009.

Cellular microenvironment is known to play a critical role in the maintenance of human bone marrow-derived mesenchymal stem cells (BM-MSCs). It was uncertain whether BM-MSCs obtained from a 'diabetic milieu' (dBM-MSCs) offer the same regenerative potential as those obtained from healthy (non-diabetic) individuals (hBM-MSCs). To investigate the effect of diabetic microenvironment on human BM-MSCs, we isolated and characterized these cells from diabetic patients (dBM-MSCs). We found that dBM-MSCs expressed mesenchymal markers such as vimentin, smooth muscle actin, nestin, fibronectin, CD29, CD44, CD73, CD90, and CD105. These cells also exhibited multilineage differentiation potential, as evident from the generation of adipocytes, osteocytes, and chondrocytes when exposed to lineage specific differentiation media. Although the cells were similar to hBM-MSCs, 6% (3/54) of dBM-MSCs expressed proinsulin/C-peptide. Emanating from the diabetic microenvironmental milieu, we analyzed whether in vitro reprogramming could afford the maturation of the islet-like clusters (ICAs) derived from dBM-MSCs. Upon mimicking the diabetic hyperglycemic niche and the supplementation of fetal pancreatic extract, to differentiate dBM-MSCs into pancreatic lineage in vitro, we observed rapid differentiation and maturation of dBM-MSCs into islet-like cell aggregates. Thus, our study demonstrated that diabetic hyperglycemic microenvironmental milieu plays a major role in inducing the differentiation of human BM-MSCs in vivo and in vitro.

Keywords: diabetes, beta-cell, stem cell, differentiation, bone marrow, NGN3, NKX6.1, PAX6

Abbreviations: -MEM - -modified Eagle's medium (used for cell culture); AGE - advanced glycation end-product; ALL - acute lymphoblastic leukemia; ALS - amyotrophic lateral sclerosis; AML - acute myeloid leukemia; BM-MSC - bone marrow-derived mesenchymal stem cell; BRN4 - Brain 4 (transcription factor expressed in the brain and glucagon-expressing cells in the pancreas, also known as POU3F4); C-peptide - connecting peptide; Ct - cycle threshold; CXCR4 - alpha-chemokine receptor (also called fusin) specific for stromal-derived-factor-1 (SDF-1, also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes; dBM-MSC - human diabetic BM-MSC; DME meduim - Dulbecco's modified Eagles medium; E-cadherin - epithelial cadherin (CDh1); EDTA - ethylenediaminetetraacetic acid (used as chelating agent that binds to calcium and prevents joining of cadher-ins between cells; it also prevents clumping of cells grown in liquid suspension, and is able to detach adherent cells for passaging); EGFP - enhanced green fluorescence protein; F(ab)2 - antigen-binding fragment of an antibody; FACS - fluorescence-activated cell sorting; GATA6 - binding protein that binds (A/T/C)GAT(A/T)(A) of the binding sequence; Glut2 - glucose transporter 2 (also known as solute carrier family 2 member 2 SLC2A2); GCG - glucagons gene; hBM-MSC - normal human BM-MSC; HD - Hodgkin disease; ICA - islet-like cell aggregate; ICAM-5 - intercellular adhesion molecule 5 (also known as telencephalin, CD# not yet assigned); ISL1 - insulin gene enhancer protein gene 1; NCAM-1 - neural cell adhesion molecule 1 (CD56); NDS - normal donkey serum; NGN-3 - neurogenin-3 (controls islet cell fate specification in pancreatic progenitor cells); NHL - non-Hodgkin lymphoma; NKX6-1 - NK6 homeobox 1 (transcription factor required for the development of beta-cells); Oil-Red-O - Solvent Red 27 (fat-soluble dye used for stain-ing of triglycerides and lipids); PBS - phosphate-buffered saline; PECAM-1 - platelet endothelial cell adhesion molecule-1 (CD31); PE - phycoerythrin (fluorescent dye for labeling antibodies); Pdx1 - pancreatic and duodenal homeobox 1 (transcription factor necessary for pancreatic development and beta-cell maturation); PFA - paraformaldehyde (used to fix cells); POU - class of genes that produce transcription factors; POU3F4 - POU class 3 homeobox 4 gene or gene product (also known as BRN4); RNA - ribonucleic acid; RPE - rat pancreatic extract; RT-PCR - reverse transcriptase polymerase chain reaction; TPVG - trypsin phosphate versene glucose; UCBS - human umbilical cord blood serum

Bone marrow-derived mesenchymal stem cells (BM-MSCs) are able to differentiate into many cell types, and to proliferate ex vivo. These attributes makes them a potential therapeutic tool for cell replacement therapy in diabetes and other diseases. Stem cell differentiation is controlled by extracellular cues, the environment, and intrinsic genetic programs within stem cells [1, 2]. The fate of stem cell differentiation is influenced by both soluble and insoluble factors from the surrounding microenvironment. Several signaling cascades mediate the balance response of the stem cell to the need of the organism. Pathological conditions induced by dysregulation result in aberrant functions of stem cells or other targets [3-6].

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TORONTO Gordie Howes son says the hockey legends stroke symptoms have improved since his treatment with stem cells at a Mexican clinic in early December and he wants him to repeat the procedure.

But regenerative medicine experts say theres no scientific evidence such therapies work, and in some cases they can be seriously harmful or even deadly.

The 86-year-old Howe suffered two disabling strokes late last year. In December, the family took him to a Tijuana clinic where he received stem cell injections as part of a clinical trial being run under a licensing agreement with Stemedica Cell Technologies of San Diego, Calif.

The experimental treatment involved injecting neural stem cells into Howes spinal canal, along with intravenous infusions of mesenchymal stem cells, which are found in bone marrow, fat and umbilical cord blood.

Marty Howe said his father can walk again, his speech is improving and he is regaining some of the weight he lost following the strokes.

After his stem cell treatment, the doctor told us it was kind of an awakening of the body, and it was all that, he told The Canadian Press while in Calgary for a hockey promotion event Tuesday. They call it the miracle of stem cells and it was nothing less than a miracle.

However, experts in the field question whether stem cells are responsible for Howes improvement and caution that most so-called stem cell therapies have not gone through rigorous scientific trials, nor have they been approved as treatments by Health Canada or the U.S. Food and Drug Administration.

Mick Bhatia, director of McMaster Universitys Stem Cell and Cancer Research Institute, said there are many unknowns in Howes case, such as how many stem cells were administered, were tests done to see whether they migrated to the targeted area of the body, and did they take up residence where they might have some effect or simply disappear?

Is this a transient effect, or is it really a perceived or somewhat of a placebo effect and is there something really happening? Scientifically and biologically that is important, Bhatia said Wednesday from Hamilton.

And because Howe received adult stem cells produced from donor cells, he may have needed to take drugs to prevent an immune reaction as well as anti-inflammatory medications, he said.

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Howes stem cell treatment raises concerns

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TORONTO - Gordie Howe's son says the hockey legend's stroke symptoms have improved since his treatment with stem cells at a Mexican clinic in early December and he wants him to repeat the procedure.

But regenerative medicine experts say there's no scientific evidence such therapies work, and in some cases they can be seriously harmful or even deadly.

The 86-year-old Howe suffered two disabling strokes late last year. In December, the family took him to a Tijuana clinic where he received stem cell injections as part of a clinical trial being run under a licensing agreement with Stemedica Cell Technologies of San Diego, Calif.

The experimental treatment involved injecting neural stem cells into Howe's spinal canal, along with intravenous infusions of mesenchymal stem cells, which are found in bone marrow, fat and umbilical cord blood.

Marty Howe said his father can walk again, his speech is improving and he is regaining some of the weight he lost following the strokes.

"After his stem cell treatment, the doctor told us it was kind of an awakening of the body, and it was all that," he told The Canadian Press while in Calgary for a hockey promotion event Tuesday. "They call it the miracle of stem cells and it was nothing less than a miracle."

However, experts in the field question whether stem cells are responsible for Howe's improvement and caution that most so-called stem cell therapies have not gone through rigorous scientific trials, nor have they been approved as treatments by Health Canada or the U.S. Food and Drug Administration.

Mick Bhatia, director of McMaster University's Stem Cell and Cancer Research Institute, said there are many unknowns in Howe's case, such as how many stem cells were administered, were tests done to see whether they migrated to the targeted area of the body, and did they take up residence where they might have some effect or simply disappear?

"Is this a transient effect, or is it really a perceived or somewhat of a placebo effect and is there something really happening? Scientifically and biologically that is important," Bhatia said Wednesday from Hamilton.

And because Howe received adult stem cells produced from donor cells, he may have needed to take drugs to prevent an immune reaction as well as anti-inflammatory medications, he said.

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Gordie Howe's stem cell therapy raises concerns among experts

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Stemologica Review - Let Your Beauty Came Out With Stemologica
Click the link below to get a risk free trial; http://skincarebeautyshop.com/go/have-your-stemologica-free-trial/ Read the Terms and Condition before you ord...

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WATCH: A new trial will use a patients own stem cells in an attempt to reduce the damage done to an MS patients nervous system. Reid Fiest has the details.

TORONTO Two Canadian research centres are gearing up for a clinical trial to determine if a type of stem cell can help alleviate the symptoms of multiple sclerosis.

Researchers at the Ottawa Hospital and Winnipegs Health Sciences Centre will each recruit 20 MS patients for the trial that will test whether mesenchymal stem cells can reduce inflammation and even help repair damage already caused by the disease.

MS is thought to be an autoimmune disease that creates inflammation in the central nervous system, resulting in injury to myelin, the protective sheath that covers nerves. This damage can create a host of symptoms, leading to varying degrees of physical disability and cognitive impairment.

Mesenchymal stem cells, which are found in bone marrow, fat, skin tissue and umbilical cord blood, have the ability to modify the immune system and reduce inflammation, said neurologist Dr. Mark Freedman of the Ottawa Hospital Research Institute, who is leading the clinical trial.

Freedman said researchers want to determine if these stem cells can demonstrate anti-inflammatory properties in patients with MS.

But thats not why were doing it, he said of the study, called MESCAMS (MEsenchymal Stem cell therapy for CAnadian MS patients). We have lots of drugs that can control inflammation in multiple sclerosis thats what all the new medicines do.

The ultimate hope is that we will be able to exploit some of their other very important biological properties, which is to promote repair.

The two research centres are ready to begin enrolling patients for the trial, which has specific acceptance criteria. While most of those accepted will likely have the relapsing-remitting form of the disease, Freedman said some people with more severe primary- or secondary-progressive MS may also be eligible if they fit the criteria.

The study protocol can be accessed at http://www.clinicaltrials.gov/show/NCT02239393. It will later be posted on the website of the MS Society of Canada, which along with the Multiple Sclerosis Scientific Research Foundation has provided a $4.2-million grant for the study.

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Trial to test stem cells in MS patients

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Stem Cell Therapy + PRP Helps Shoulder Injury and Whiplash Patient - Denise Lawson
Denise Lawson experienced two motor vehicle accidents in 2001 that left her with neck pain, headaches, and sporadic episodes of weakness on the left side of her body. Over time, Denise developed...

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