Washington, Mar 19 (ANI): A compound used in traditional Japanese medicine, honokiol (HNK), plays a role in blocking key protein in inflammatory brain damage, a new study led by Indian origin scientist has suggested.

Microglia are the first line defence of the brain and are constantly looking for infections to fight off.

Overactive microglia can cause uncontrolled inflammation within the brain, which can in turn lead to neuronal damage.

New research shows that HNK is able to down-regulate the production of pro-inflammatory cytokines and inflammatory enzymes in activated microglia via Klf4, a protein known to regulate DNA.

Scientists from the National Brain Research Centre, Manesar, India, used lipopolysaccharide (LPS), a molecule present on the surface of bacteria, to stimulate an immune response from microglia cells.

LPS mimics the effect of a bacterial infection and the microglia cells spring into action, releasing proinflammatory cytokines, such as TNFa.

Activation of microglia also stimulates the production of nitric oxide (NO) and Cox-2, which co-ordinate the immune response, leading to inflammation.

However uncontrolled inflammation can lead to neuronal death and permanent brain damage.

Microglial inflammation is also observed in several neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and multiple sclerosis.

The team led by Dr Anirban Basu found that the inflammatory response was mediated by Klf4, a 'transcription' factor which binds directly to DNA to enhance or impede gene expression.

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Japanese traditional therapy may help prevent inflammatory brain damage

Recommendation and review posted by Bethany Smith

London, March 19 (ANI): Researchers have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain, which results in obesity caused by a voracious appetite.

Researchers at Georgetown University Medical Center suggested there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain.

In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," said the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown.

"This discovery may open up novel strategies to help the brain control body weight," he noted.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them.

The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

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Gluttony gene that makes you eat more even when you are full identified

Recommendation and review posted by Bethany Smith

A single gene's effect on the brain can result in non-stop eating, research has shown.

Scientists believe the "gluttony gene" may be responsible for cases of obesity caused by out-of-control appetite.

The Bdnf gene variant was studied in mice. It was found to prevent brain neurons from transmitting signals that tell the body it has eaten enough.

"This discovery may open up novel strategies to help the brain control body weight," said lead researcher Dr Baoki Xu, from Georgetown University Medical Centre in the United States.

Hunger and satiety, the sensation of "feeling full", are governed by a complex balance of hormonal and neuronal signals.

Two hormones in particular, leptin and insulin, released in the body after a meal play a key role.

Their chemical signals activate neurons in the hypothalamus region of the brain that trigger satiety. But if the connection is not made, the craving for food continues.

"Short" versions of the Bdnf gene block the leptin and insulin signals and prevent the "stop eating" message passing through the brain to the correct appetite-suppressing locations, say the scientists.

The research is reported in the journal Nature Medicine.

Bdnf makes a protein that is synthesised in dendrites, the branch-like "fingers" that project from nerve cells. Dendrites carry the synapses that neurons use to communicate to each other.

The rest is here:
'Gluttony gene' may explain out-of-control appetite

Recommendation and review posted by Bethany Smith

At 102, Saul Belson has escaped many of the diseases that easily kill men 30 and 40 years his junior.

It may be luck, or the fact that he tried to eat healthy and was never a smoker or a drinker. Or, it might be genetics.

Belson is part of a set of those not just living, but living life well and with no or few health problems, over age 100.

Hes hoping to be selected as a genomic pioneer in a gene sequencing competition.

A hundred centenarians are being chosen worldwide to voluntarily contribute their DNA to the Archon Genomics X PRIZE competition, presented by Medco, a health care and research company based in New Jersey.

It is a competition of world-class teams from genotyping companies that will compete to quickly, accurately and affordably sequence the genomes of the 100 centenarians.

The grand prize to the winning genotyping company is $10 million. It is being funded by philanthropists and sponsors.

Ive always been very interested in science, Belson said. If Ive got something good, Im willing to share it.

Belson was born in London on Sept. 12, 1909, to Russian immigrant parents. They came to Chicago when he was 5 years old.

Belson spent most of his professional life working in the dental industry as a designer, making false teeth for Boston Dental in Chicago. He moved to Sakonnet Bay Manor in Tiverton six years ago after his wife, Dora, died, and to be closer to his son, Harold.

Follow this link:
Tiverton centenarian recruited for genetics contest that could unlock secrets of longevity

Recommendation and review posted by Bethany Smith

London, March 19 (ANI): Scientists have now found answer to why some patients fail to respond to some of the most successful cancer drugs.

Tyrosine kinase inhibitor drugs (TKIs) work effectively in most patients to fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene.

These precisely targeted drugs shut down molecular pathways that keep these cancers flourishing and include TKIs for treating CML, and the form of NSCLC with EGFR genetic mutations.

Now, a multi-national research team led by scientists at Duke-NUS Graduate Medical School in Singapore, working with the Genome Institute of Singapore (GIS), Singapore General Hospital and the National Cancer Centre Singapore, has discovered that there is a common variation in the BIM gene in people of East Asian descent that contributes to some patients' failure to benefit from these tyrosine kinase inhibitor drugs.

"Because we could determine in cells how the BIM gene variant caused TKI resistance, we were able to devise a strategy to overcome it," said S. Tiong Ong, M.B.B. Ch., senior author of the study and associate professor in the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS and Division of Medical Oncology, Department of Medicine, at Duke University Medical Center.

"A novel class of drugs called the BH3-mimetics provided the answer," he said.

"When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients," Ong added.

Yijun Ruan, Ph.D., a co-senior author of this study and associate director for Genome Technology and Biology at GIS said: "We used a genome-wide sequencing approach to specifically look for structural changes in the DNA of patient samples. This helped in the discovery of the East Asian BIM gene variant. What's more gratifying is that this collaboration validates the use of basic genomic technology to make clinically important discoveries."

If the drug combination does override TKI resistance in people, this will be good news for those with the BIM gene variant, which occurs in about 15 percent of the typical East Asian population. By contrast, no people of European or African ancestry were found to have this gene variant.

"While it's interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations," said Patrick Casey, Ph.D., senior vice dean for research at Duke-NUS and James B. Duke Professor of Pharmacology and Cancer Biology.

Read the rest here:
Gene variant in East Asians could explain resistance to cancer drugs

Recommendation and review posted by Bethany Smith

LOS ANGELES, Calif. - The creation of California's stem cell agency in 2004 was greeted by scientists and patients as a turning point in a field mired in debates about the destruction of embryos and hampered by federal research restrictions.

The taxpayer-funded institute wielded the extraordinary power to dole out $3 billion in bond proceeds to fund embryonic stem cell work with an eye toward treatments for a host of crippling diseases. Midway through its mission, with several high-tech labs constructed, but little to show on the medicine front beyond basic research, the California Institute for Regenerative Medicine faces an uncertain future.

Is it still relevant nearly eight years later? And will it still exist when the money dries up?

The answers could depend once again on voters and whether they're willing to extend the life of the agency.

Several camps that support stem cell research think taxpayers should not pay another cent given the state's budget woes.

"It would be so wrong to ask Californians to pony up more money," said Marcy Darnovsky of the Center for Genetics and Society, a pro-stem cell research group that opposed Proposition 71, the state ballot initiative that formed CIRM.

Last December, CIRM's former chairman, Robert Klein, who used his fortune and political connections to create Prop 71, floated the possibility of another referendum.

CIRM leaders have shelved the idea of going back to voters for now, but may consider it down the road. The institute recently submitted a transition plan to Gov. Jerry Brown and the Legislature that assumes it will no longer be taxpayer-supported after the bond money runs out. CIRM is exploring creating a non-profit version of itself and tapping other players to carry on its work.

"The goal is to keep the momentum going," board Chairman Jonathan Thomas said in an interview.

So far, CIRM has spent some $1.3 billion on infrastructure and research. At the current pace, it will earmark the last grants in 2016 or 2017. Since most are multi-year awards, it is expected to stay in business until 2021.

View post:
California's stem cell agency ponders a future without taxpayer support

Recommendation and review posted by simmons

LOS ANGELES (AP) The creation of California's stem cell agency in 2004 was greeted by scientists and patients as a turning point in a field mired in debates about the destruction of embryos and hampered by federal research restrictions.

The taxpayer-funded institute wielded the extraordinary power to dole out $3 billion in bond proceeds to fund embryonic stem cell work with an eye toward treatments for a host of crippling diseases. Midway through its mission, with several high-tech labs constructed, but little to show on the medicine front beyond basic research, the California Institute for Regenerative Medicine faces an uncertain future.

Is it still relevant nearly eight years later? And will it still exist when the money dries up?

The answers could depend once again on voters and whether they're willing to extend the life of the agency.

Several camps that support stem cell research think taxpayers should not pay another cent given the state's budget woes.

"It would be so wrong to ask Californians to pony up more money," said Marcy Darnovsky of the Center for Genetics and Society, a pro-stem cell research group that opposed Proposition 71, the state ballot initiative that formed CIRM.

Last December, CIRM's former chairman, Robert Klein, who used his fortune and political connections to create Prop 71, floated the possibility of another referendum.

CIRM leaders have shelved the idea of going back to voters for now, but may consider it down the road. The institute recently submitted a transition plan to Gov. Jerry Brown and the Legislature that assumes it will no longer be taxpayer-supported after the bond money runs out. CIRM is exploring creating a nonprofit version of itself and tapping other players to carry on its work.

"The goal is to keep the momentum going," board Chairman Jonathan Thomas said in an interview.

So far, CIRM has spent some $1.3 billion on infrastructure and research. At the current pace, it will earmark the last grants in 2016 or 2017. Since most are multi-year awards, it is expected to stay in business until 2021.

Read more here:
California's stem cell agency ponders its future

Recommendation and review posted by simmons

For about three days in January, Matt Ladd said he didnt know whether it was day or night, what was top or bottom.

I was probably as sick as Ive ever been, said Ladd, a Billings game warden, in a telephone interview from Seattle. As things got progressively worse and worse, I was really concerned about what was going on right then.

Ladd was headed to Seattle for stem cell bone marrow transplant surgery when an infection he was being treated for worsened. The infection started around a catheter inserted into his chest to deliver chemotherapy drugs. The chemo was battling Ladds acute myeloid leukemia and myelodysplastic syndrome, which was diagnosed in September. His bone marrow wasnt producing enough red blood cells.

The chemo worked. He was in remission and on his way to Seattle for a bone marrow transplant when the infection sent him into a rapid downward spiral. Because of the location of the catheter, the infection attacked his heart valves. During the struggle with the infection, his kidneys failed, his body retained water and he swelled up.

The infection scuttled plans for the bone marrow transplant surgery. With his kidneys failing, he had to undergo dialysis. As a final insult to his immune system, he had to take more chemotherapy since the surgery had been delayed and doctors feared the MDS might return.

My body and kidneys didnt respond well to the chemo, he said.

More than a month after he was scheduled to undergo surgery, Ladd is living in an apartment north of Seattle as family members rotate caretaking duties. His wife, Maureen, a math teacher at Billings West High, is holding down the fort at home, trying to maintain a sense of normalcy for their sons, Dylan, Logan and Jack.

What was going to be a short process has become a very long process, Maureen said.

Now the Ladds are waiting to hear whether Matt and his sister, Jessica Cook, will take part in a Seattle Cancer Center Alliance study of a new method of bone marrow transplantation. Since Ladds kidneys have been injured, he would normally have to have a reduced-intensity transplant used for the elderly and those with health issues, Maureen explained.

The experimental method would treat Cook, Ladds only sibling and a bone marrow transplant match, with Lipitor prior to the surgery. The cholesterol-lowering drug has shown promise in preventing reactions to transplants. If they are accepted for the study, it would mean a further delay of surgery, since Cook would have to be on the drug for a couple of weeks prior to the operation.

Read more from the original source:
Billings game warden fights cancer complications

Recommendation and review posted by Bethany Smith

For David and Mary Hubbell of Fisher, every day spent with their 18-year-old daughter, Katy, feels like a treasure.

Katy Hubbell was 4 years old in 1997 when doctors diagnosed her with a life-threatening bone marrow disease called aplastic anemia.

The disease prevented Katy's body from producing enough blood cells to keep her alive, and at least one doctor gave the Fisher girl a year to live.

But Katy and her family received new hope when she received a bone marrow transplant in Houston, followed by rounds of chemotherapy treatment. Community members offered their prayers and put on fundraisers to help pay for the family's bills.

Nearly 13 years after the life-changing procedure, Katy Hubbell is a senior at Fisher High School, where she has a part in the school play, completes anime drawings and plans to go to college.

"Katy continues to amaze us, and every day with this smiling girl is a gift," said Katy's mother, Mary Hubbell. "The experience changed us as people and made us realize that life is so short."

David Hubbell took his daughter to a pediatrician at Carle after she began receiving an abnormal number of bruises in 1997. Blood tests showed Katy's platelet level was dangerously low.

When her red and white cell counts started to fall, Katy was transferred to Children's Memorial Hospital in Chicago, where she was diagnosed with aplastic anemia, along with lymphoma.

"Patients with severe aplastic anemia have no immune system," Mary Hubbell said. "They can't be outside of a hospital environment, and any kind of infection can be very life-threatening."

Katy was kept at home to avoid infection, and visitors had to scrub themselves before entering the home.

More:
13 years after a bone-marrow transplant, Katy Hubbell plans for college

Recommendation and review posted by Bethany Smith

Rett syndrome, an autism spectrum disorder, causes problems with communication, coordination and movement.

AP Photo/The Idaho Statesman

A bone-marrow transplant can treat a mouse version of Rett syndrome, a severe autism spectrum disorder that affects roughly 1 in 10,00020,000 girls born worldwide (boys with the disease typically die within a few weeks of birth).

The findings, published today in Nature1, suggest that brain-dwelling immune cells called microglia are defective in Rett syndrome. The authors say their findings also raise the possibility that bone-marrow transplants or other means of boosting the brains immune cells could help to treat the disease.

If we show the immune system is playing a very important role in Rett patients and we could replace it in a safe way, we may develop some feasible therapies in the future, says Jonathan Kipnis, a neuroscientist at the University of Virginia School of Medicine in Charlottesville, who led the study.

Mutations in a single gene on the X chromosome,MECP2, cause the disease. Because they have only one X chromosome, boys born with the mutation die within weeks of birth. Girls with one faulty copy develop Rett syndrome.

Symptoms of Rett syndrome typically set in between 6 and 18 months of age. Girls with the disease have trouble putting on weight and often do not learn to speak. They repeat behaviours such as hand-washing and tend to have trouble walking. Many develop breathing problems and apnoea. Rett syndrome is classified as an autism spectrum disorder, and treatments focus on symptoms such as nutritional and gastrointestinal problems.

The MECP2 protein orchestrates the activity of many other genes, but how its alteration causes Rett syndrome is a mystery. I wish I knew, says Kipnis.

Neurons express more MECP2 than any other cell in the brain, and restoring the genes function in mouse neurons reverses some disease symptoms2.Recently, however, scientists have begun to suspect that other brain cells are also involved. Re-activating MECP2 in brain-support cells called astrocytes treats gait problems and anxiety in mice3.

Kipnis and his team focused on another class of brain cell microglia. They are the brains macrophages, a type of immune cell that sops up the detritus created by other cells. Studies have linked various immune cells to brain function, including repetitive and compulsive behaviour4, which led Kipnis to test whether replacing an immune system in mice lacking Mecp2 with cells containing the gene could improve symptoms.

Continued here:
Bone-marrow transplant reverses Rett syndrome in mice

Recommendation and review posted by Bethany Smith

Among the primary causes of adult-onset blindness are degenerative diseases of the retina, such as macular degeneration and retinitis pigmentosa. While some treatments have been developed that slow down the rate of degeneration, the clinical situation is still generally unsatisfactory. But if you could grow a new retina, transplant might be a possible cure. Now new hope is springing up from a research project at the University of Wisconsin-Madison in which scientists have succeeded in growing human retinal tissue from stem cells.

Pluripotent stem cells are capable of forming nearly any tissue in the body including retinal tissue. There has been great controversy about using pluripotent stem cells for human research or treatment, as historically the only source was to harvest them from early stage human embryos. Instead, for this work the researchers were able to regress mature body cells back into the pluripotent stem cells from which they originally grew. The process is called reprogramming, and is accomplished by inserting a set of proteins into the cell.

To produce the pluripotent stem cells, a white blood cell was taken from a simple blood sample. Genes which code for the reprogramming proteins are inserted into a plasmid, a nonliving ring of DNA. The cell is then infected with the plasmid, rather as a virus infects a cell, with the difference that the plasmid's genes do not become part of the cell's genetic structure. As the reprogramming proteins are formed within the cell by the plasmid DNA, the cell has a good chance of being reprogrammed into a pluripotent stem cell. This stem cell can then be encouraged to grow and differentiate into retinal tissue rather than make more blood cells.

Laboratory-grown human retinal tissue will certainly be used in testing drugs and to study degenerative diseases of the retina, and may eventually make available a new transplantable retina, or a new retina that is grown in place within the eye.

The figure above compares a schematic of the human retina with a photomicrograph of laboratory-grown retinal tissue. The new tissue has separated into at least three layers of cells, with rudimentary photosensitive rods or cones (red) at the top of the picture, and nerve ganglia (blue-green) at the bottom. The blue cells in the middle layer are likely bipolar retinal cells. The structure of the lab-grown retinal tissue is similar to that of a normal human eye, as can be seen by comparison with the retina schematic. The cells also formed synapses, which provide the channels through which optical information flows to the brain.

"We don't know how far this technology will take us, but the fact that we are able to grow a rudimentary retina structure from a patient's blood cells is encouraging, not only because it confirms our earlier work using human skin cells, but also because blood as a starting source is convenient to obtain," says Dr. David Gamm, pediatric ophthalmologist and senior author of the study. "This is a solid step forward." Further steps are eagerly awaited by those living in the dark.

Source: University of Wisconsin School of Medicine and Public Health

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Physicians grow retinas from human blood-derived stem cells

Recommendation and review posted by Bethany Smith

Could lead to treatments for obesity

By Tamara Cohen

PUBLISHED: 14:28 EST, 18 March 2012 | UPDATED: 14:28 EST, 18 March 2012

The secret to staying slim may be all in your genes.

Scientists believe they have found the gluttony gene which fails to tell your brain when you are full.

In tests on mice, they showed that a mutation on a single gene broke down communication in the body and led to non-stop eating and rapid weight gain.

Gut buster: Scientists believe they have uncovered a gene which makes you eat even when are full because it breaks down communication between the body and the brain

But the good news is, they hope identifying the gene could help with treatments for obesity which affects nearly one in four adults in the UK.

Researchers at Georgetown University Medical Centre in the U.S. studied variations in the Bdnf gene in mice.

See original here:
Georgetown University Medical Centre: Scientists discover 'greedy gene¿ that makes you eat more even when you are full

Recommendation and review posted by Bethany Smith

A single gene's effect on the brain can result in non-stop eating, research has shown.

Scientists believe the "gluttony gene" may be responsible for cases of obesity caused by out-of-control appetite. The Bdnf gene variant was studied in mice. It was found to prevent brain neurons from transmitting signals that tell the body it has eaten enough.

"This discovery may open up novel strategies to help the brain control body weight," said lead researcher Dr Baoki Xu, from Georgetown University Medical Centre in the US.

Hunger and satiety, the sensation of "feeling full", are governed by a complex balance of hormonal and neuronal signals. Two hormones in particular, leptin and insulin, released in the body after a meal play a key role.

Their chemical signals activate neurons in the hypothalamus region of the brain that trigger satiety. But if the connection is not made, the craving for food continues.

"Short" versions of the Bdnf gene block the leptin and insulin signals and prevent the "stop eating" message passing through the brain to the correct appetite-suppressing locations, say the scientists.

The research is reported online in the journal Nature Medicine.

Bdnf makes a protein that is synthesised in dendrites, the branch-like "fingers" that project from nerve cells. Dendrites carry the synapses that neurons use to communicate to each other.

"If there is a problem with the Bdnf gene, neurons can't talk to each other and the leptin and insulin signals are ineffective, and appetite is not modified," said Dr Xu.

Previous work by Dr Xu has shown that Bdnf is important for the formation and maturation of synapses during development. Mice born without the correct "long" version of the gene suffer impaired learning and memory. They also grow to be severely obese.

Read more:
Scientists 'discover gluttony gene'

Recommendation and review posted by Bethany Smith

This is a guest post from M. A. Loera Snchez from the iGEM team UANL 2012. I have carried out a few small grammar edits but otherwise the essay is all his work, and I would like to thank him for the opportunity to host it on my blog. All references are below the main text.

The mainstream fronts of synthetic biology

What I cannot build, I cannot understand.

This phrase by the genius physicist Richard Feynman is cleverly encrypted into the genetic code of the first bacterial cells with an artificial genome that have ever existed.

Actually the quote says what I cannot create, but maybe the scientists at the JCVI who are behind this tremendous breakthrough- preferred to save some base pairs to avoid the use of the word create and its tricky implications.They published this work in 2010 and opened a whole new world of possibilities and made it completely clear to anyone what we mean when we talk about Synthetic Biology and what its ultimate purpose should be: to understand life by building it.

Although the term Synthetic Biology has been around since the mid-1970s, the definition of it has been very vague: some people would call Synthetic Biology anything related to general genetic engineering procedures; others, perhaps more rightfully, would claim to be doing Synthetic Biology because of working with DNA synthesis or making bacteria behave like tiny computers. Even the 2010 report by the US Presidencial Comission for the Study of Bioethical Issues has to define the term considering different points of view (that of the molecular biology, the chemist and the engineer) and states that the activities related to Synthetic Biology are considered by some to be just extensions of already existing fields, like Molecular Biology, Genetic Engineering and Microbiology.

I remember (oh, the shame!) being skeptic about the possibility of something so oxymoronic being, well true. I still turn red when I recall that I kind of corrected the person who first said Synthetic Biology to me by telling her that what she wanted to say was maybe Systems Biology.

So what is it really?

Well, my work in Bio! has been devoted to dig into the deeps of Synthetic Biology and the iGEM competition, and throughout this time I began to notice what I would call the mainstream fronts of Synthetic Biology. These are the main orientations that so called Synthetic Biology projects would take and by enlisting them, I think it will be easier to clarify the distinctive characteristics of this field.

Front 1: DNA synthesis

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The mainstream fronts of Synthetic Biology: Guest post

Recommendation and review posted by Bethany Smith

ScienceDaily (Mar. 18, 2012) A multinational research team led by scientists at Duke-NUS Graduate Medical School has identified the reason why some patients fail to respond to some of the most successful cancer drugs.

Tyrosine kinase inhibitor drugs (TKI) work effectively in most patients to fight certain blood cell cancers, such as chronic myelogenous leukemia (CML), and non-small-cell lung cancers (NSCLC) with mutations in the EGFR gene.

These precisely targeted drugs shut down molecular pathways that keep these cancers flourishing and include TKIs for treating CML, and the form of NSCLC with EGFR genetic mutations.

Now the team at Duke-NUS Graduate Medical School in Singapore, working with the Genome Institute of Singapore (GIS), Singapore General Hospital, and the National Cancer Centre Singapore, has discovered that there is a common variation in the BIM gene in people of East Asian descent that contributes to some patients' failure to benefit from these tyrosine kinase inhibitor drugs.

"Because we could determine in cells how the BIM gene variant caused TKI resistance, we were able to devise a strategy to overcome it," said S. Tiong Ong, MBBCh, senior author of the study and associate professor in the Cancer and Stem Cell Biology Signature Research Programme at Duke-NUS and Division of Medical Oncology, Department of Medicine, at Duke University Medical Center.

"A novel class of drugs called the BH3-mimetics provided the answer," Ong said. "When the BH3 drugs were added to the TKI therapy in experiments conducted on cancer cells with the BIM gene variant, we were able to overcome the resistance conferred by the gene. Our next step will be to bring this to clinical trials with patients."

Said Yijun Ruan, PhD, a co-senior author of this study and associate director for Genome Technology and Biology at GIS: "We used a genome-wide sequencing approach to specifically look for structural changes in the DNA of patient samples. This helped in the discovery of the East Asian BIM gene variant. What's more gratifying is that this collaboration validates the use of basic genomic technology to make clinically important discoveries."

The study was published online in Nature Medicine on March 18.

If the drug combination does override TKI resistance in people, this will be good news for those with the BIM gene variant, which occurs in about 15 percent of the typical East Asian population. By contrast, no people of European or African ancestry were found to have this gene variant.

"While it's interesting to learn about this ethnic difference for the mutation, the greater significance of the finding is that the same principle may apply for other populations," said Patrick Casey, PhD, senior vice dean for research at Duke-NUS and James B. Duke Professor of Pharmacology and Cancer Biology.

See original here:
Genetic variation in East Asians found to explain resistance to cancer drugs

Recommendation and review posted by Bethany Smith

Public release date: 18-Mar-2012 [ | E-mail | Share ]

Contact: Karen Mallet km463@georgetown.edu Georgetown University Medical Center

Washington, D.C. -- Researchers at Georgetown University Medical Center have revealed how a mutation in a single gene is responsible for the inability of neurons to effectively pass along appetite suppressing signals from the body to the right place in the brain. What results is obesity caused by a voracious appetite.

Their study, published March 18th on Nature Medicine's website, suggests there might be a way to stimulate expression of that gene to treat obesity caused by uncontrolled eating.

The research team specifically found that a mutation in the brain-derived neurotrophic factor (Bdnf) gene in mice does not allow brain neurons to effectively pass leptin and insulin chemical signals through the brain. In humans, these hormones, which are released in the body after a person eats, are designed to "tell" the body to stop eating. But if the signals fail to reach correct locations in the hypothalamus, the area in the brain that signals satiety, eating continues.

"This is the first time protein synthesis in dendrites, tree-like extensions of neurons, has been found to be critical for control of weight," says the study's senior investigator, Baoji Xu, Ph.D., an associate professor of pharmacology and physiology at Georgetown.

"This discovery may open up novel strategies to help the brain control body weight," he says.

Xu has long investigated the Bdnf gene. He has found that the gene produces a growth factor that controls communication between neurons.

For example, he has shown that during development, BDNF is important to the formation and maturation of synapses, the structures that permit neurons to send chemical signals between them. The Bdnf gene generates one short transcript and one long transcript. He discovered that when the long-form Bdnf transcript is absent, the growth factor BDNF is only synthesized in the cell body of a neuron but not in its dendrites. The neuron then produces too many immature synapses, resulting in deficits in learning and memory in mice.

Xu also found that the mice with the same Bdnf mutation grew to be severely obese.

See the original post:
Researchers reveal how a single gene mutation leads to uncontrolled obesity

Recommendation and review posted by Bethany Smith

For David and Mary Hubbell of Fisher, every day spent with their 18-year-old daughter, Katy, feels like a treasure.

Katy Hubbell was 4 years old in 1997 when doctors diagnosed her with a life-threatening bone marrow disease called aplastic anemia.

The disease prevented Katy's body from producing enough blood cells to keep her alive, and at least one doctor gave the Fisher girl a year to live.

But Katy and her family received new hope when she received a bone marrow transplant in Houston, followed by rounds of chemotherapy treatment. Community members offered their prayers and put on fundraisers to help pay for the family's bills.

Nearly 13 years after the life-changing procedure, Katy Hubbell is a senior at Fisher High School, where she has a part in the school play, completes anime drawings and plans to go to college.

"Katy continues to amaze us, and every day with this smiling girl is a gift," said Katy's mother, Mary Hubbell. "The experience changed us as people and made us realize that life is so short."

David Hubbell took his daughter to a pediatrician at Carle after she began receiving an abnormal number of bruises in 1997. Blood tests showed Katy's platelet level was dangerously low.

When her red and white cell counts started to fall, Katy was transferred to Children's Memorial Hospital in Chicago, where she was diagnosed with aplastic anemia, along with lymphoma.

"Patients with severe aplastic anemia have no immune system," Mary Hubbell said. "They can't be outside of a hospital environment, and any kind of infection can be very life-threatening."

Katy was kept at home to avoid infection, and visitors had to scrub themselves before entering the home.

Read the rest here:
13 years after a bone-marrow transplant, Katy Hubbell plans for college

Recommendation and review posted by sam

Rett syndrome, an autism spectrum disorder, causes problems with communication, coordination and movement.

AP Photo/The Idaho Statesman

A bone-marrow transplant can treat a mouse version of Rett syndrome, a severe autism spectrum disorder that affects roughly 1 in 10,00020,000 girls born worldwide (boys with the disease typically die within a few weeks of birth).

The findings, published today in Nature1, suggest that brain-dwelling immune cells called microglia are defective in Rett syndrome. The authors say their findings also raise the possibility that bone-marrow transplants or other means of boosting the brains immune cells could help to treat the disease.

If we show the immune system is playing a very important role in Rett patients and we could replace it in a safe way, we may develop some feasible therapies in the future, says Jonathan Kipnis, a neuroscientist at the University of Virginia School of Medicine in Charlottesville, who led the study.

Mutations in a single gene on the X chromosome,MECP2, cause the disease. Because they have only one X chromosome, boys born with the mutation die within weeks of birth. Girls with one faulty copy develop Rett syndrome.

Symptoms of Rett syndrome typically set in between 6 and 18 months of age. Girls with the disease have trouble putting on weight and often do not learn to speak. They repeat behaviours such as hand-washing and tend to have trouble walking. Many develop breathing problems and apnoea. Rett syndrome is classified as an autism spectrum disorder, and treatments focus on symptoms such as nutritional and gastrointestinal problems.

The MECP2 protein orchestrates the activity of many other genes, but how its alteration causes Rett syndrome is a mystery. I wish I knew, says Kipnis.

Neurons express more MECP2 than any other cell in the brain, and restoring the genes function in mouse neurons reverses some disease symptoms2.Recently, however, scientists have begun to suspect that other brain cells are also involved. Re-activating MECP2 in brain-support cells called astrocytes treats gait problems and anxiety in mice3.

Kipnis and his team focused on another class of brain cell microglia. They are the brains macrophages, a type of immune cell that sops up the detritus created by other cells. Studies have linked various immune cells to brain function, including repetitive and compulsive behaviour4, which led Kipnis to test whether replacing an immune system in mice lacking Mecp2 with cells containing the gene could improve symptoms.

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Bone-marrow transplant reverses Rett syndrome in mice

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29-02-2012 15:30 Scientists have created cerebral cortex cells-- those that make up the brain's gray matter-- from a small sample of skin. Source: Cambridge Read more: http://www.laboratoryequipment.com

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13-03-2012 19:50 Produced by the Department of Physical Medicine and Rehabilitation at the University of Rochester Medical Center, this video illustrates how 5 people living with spinal cord injury have modified their homes. Visit us on the web at http://www.urmc.rochester.edu This video was funded by the Craig H. Neilsen Foundation.

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Home modifications following a spinal cord injury - Video

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For about three days in January, Matt Ladd said he didnt know whether it was day or night, what was top or bottom.

I was probably as sick as Ive ever been, said Ladd, a Billings game warden, in a telephone interview from Seattle. As things got progressively worse and worse, I was really concerned about what was going on right then.

Ladd was headed to Seattle for stem cell bone marrow transplant surgery when an infection he was being treated for worsened. The infection started around a catheter inserted into his chest to deliver chemotherapy drugs. The chemo was battling Ladds acute myeloid leukemia and myelodysplastic syndrome, which was diagnosed in September. His bone marrow wasnt producing enough red blood cells.

The chemo worked. He was in remission and on his way to Seattle for a bone marrow transplant when the infection sent him into a rapid downward spiral. Because of the location of the catheter, the infection attacked his heart valves. During the struggle with the infection, his kidneys failed, his body retained water and he swelled up.

The infection scuttled plans for the bone marrow transplant surgery. With his kidneys failing, he had to undergo dialysis. As a final insult to his immune system, he had to take more chemotherapy since the surgery had been delayed and doctors feared the MDS might return.

My body and kidneys didnt respond well to the chemo, he said.

More than a month after he was scheduled to undergo surgery, Ladd is living in an apartment north of Seattle as family members rotate caretaking duties. His wife, Maureen, a math teacher at Billings West High, is holding down the fort at home, trying to maintain a sense of normalcy for their sons, Dylan, Logan and Jack.

What was going to be a short process has become a very long process, Maureen said.

Now the Ladds are waiting to hear whether Matt and his sister, Jessica Cook, will take part in a Seattle Cancer Center Alliance study of a new method of bone marrow transplantation. Since Ladds kidneys have been injured, he would normally have to have a reduced-intensity transplant used for the elderly and those with health issues, Maureen explained.

The experimental method would treat Cook, Ladds only sibling and a bone marrow transplant match, with Lipitor prior to the surgery. The cholesterol-lowering drug has shown promise in preventing reactions to transplants. If they are accepted for the study, it would mean a further delay of surgery, since Cook would have to be on the drug for a couple of weeks prior to the operation.

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Billings game warden fights cancer complications

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SHAPE Urges NIH to Adopt Personalized Medicine for Heart Attack Prevention

Houston, TX (PRWEB) March 17, 2012

One of the most important developments is the use of noninvasive imaging to diagnose atherosclerosis in its pre-symptomatic stage. While detection and treatment of traditional risk factors such as high cholesterol and high blood pressure are important, it is now clear that the direct measurement of atherosclerosis, which enables personalized risk assessment, is useful in identifying high risk individuals and improves risk classification.

In fact, in the 9 years since the NIH released NCEP-III Guidelines which introduced Global Risk Assessment, subclinical atherosclerosis has gained increased recognition as a more powerful predictor than all risk factor combinations and risk factor-based scoring systems. The burden of atherosclerotic plaques predicts adverse events much more accurately than risk factors, particularly near-term events.

Consequently, in 2009, the Appropriate Use Criteria considered coronary artery calcium scans (CAC) appropriate for asymptomatic patients with an Intermediate global risk estimate, as well as those deemed lower risk with a family history of premature coronary heart disease. In 2010, the ACC/AHA Guideline for Assessment of Cardiovascular Risk in Asymptomatic Adults followed suit, elevating CAC and carotid plaque and intima-media thickness (CIMT) to Class IIa recommendations for cardiovascular risk assessment in asymptomatic adults at intermediate (10% to 20% 10-year) risk.

As we await the NCEP IV Guidelines, the SHAPE Task Force anticipates that the discoveries of the past decade will be incorporated in the NCEP Adult Treatment Panel (ATP) IV, and that the NIH will assign a major role to detection of subclinical atherosclerosis to improve risk prediction for primary prevention of atherosclerotic cardiovascular disease.

The Guidelines should no longer favor intensive treatment of cholesterol independent of atherosclerosis, but instead must target those individuals with the highest burden of atherosclerotic CVD risk who are expected to benefit the most from aggressive cholesterol-lowering therapies. The heightened awareness of possible statin induced hyperglycemia (diabetes mellitus) and rare cognitive dysfunction reinforces the need for more accurate risk assessment to insure that widespread drug therapy is appropriately implemented.

The SHAPE Task Force therefore suggests changing the name of the National Cholesterol Education Program to the National Atherosclerosis Education Program. This change will appropriately shift the focus from a single risk factor of atherosclerosis (cholesterol) to atherosclerosis itself, and can help save the lives of many High Risk individuals, who are currently misclassified as Low or Intermediate Risk.

SHAPE is continuing its scientific quest for innovative approaches to heart attack prevention, and ultimately, eradication. As an educational nonprofit organization, SHAPE advocates only the most scientifically proven approach, independent of specific practices or procedures. SHAPE is actively supporting the Department of Health & Human Services Million Hearts initiative to prevent one million heart attacks and strokes over five years.

Members of the SHAPE Task Force include:

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SHAPE Task Force Calls for Changing National Cholesterol Education Program (NCEP) to National Atherosclerosis ...

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28-12-2011 05:37 Ceraxon Citicoline - link to online store GenuineTabs.com Modafinil (Modalert) 100 mg / 200 mg Modalert (modafinil) is a medication that promotes wakefulness. It is thought to work by altering the natural chemicals (neurotransmitters) in the brain. The best quality of smart drugs ceraxon...

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Washington, March 17 (ANI): New biotechnological and chemical methods will facilitate efficient production of chemicals, materials and fuels from renewable natural resources, such as agricultural or industrial waste materials, say researchers.

The Academy of Finland Centre of Excellence (CoE) in White Biotechnology - Green Chemistry Research is focusing on the research and development of microbial cells, or cell factories, for producing new useful compounds from sugars in plant biomass.

These compounds can be used, for example, for manufacturing bioplastics or in medical applications.

"By means of gene technology, we can modify microbial metabolism and thereby produce organic acids for a wide range of industrial applications. They can be used, among other things, for manufacturing new plastic and textile materials, or packaging technologies," explained Merja Penttila, Research Professor and Director of the Centre of Excellence from VTT Technical Research Centre of Finland.

New methods play a key role when various industries are developing environmentally friendly and energy-efficient production processes.

Use of renewable natural resources, such as agricultural or industrial waste materials, to replace oil-based raw materials will make industries less dependent of fossil raw materials and, consequently, reduce carbon dioxide emissions into the atmosphere.

The CoE also develops highly sensitive measuring methods and investigates microbial cell functions at molecular level.

"We need this information to be able to develop efficient bioprocesses for the future. For instance, we build up new micro- and nanoscale instruments for measuring and controlling microbial productivity in bioreactors during production," said Penttila.

The metabolism of microbes is modified so that they will convert plant biomass sugars into sugar acids and their derivatives.

These compounds can potentially serve as raw materials for new types of polyesters, whose properties - such as water solubility and extremely rapid degradation into natural substances - can be used, for example, in medicine.

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Soon, gene technology to produce novel plastics and textiles from waste

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18-02-2011 06:00 What is the difference between stem cell transplantation and bone marrow transplantation?

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Bone Marrow Transplantation: Stem Cell Transplantation - Video

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