Archive for the ‘Gene Therapy Research’ Category

ScienceDaily (Aug. 27, 2012) Some of the body's own genetic material, known as small interfering RNA (siRNA), can be packaged then unleashed as a precise and persistent technology to guide cell behavior, researchers at Case Western Reserve University report in the current issue of the journal, Acta Biomaterialia.

The research group, led by Eben Alsberg, associate professor in the departments of Biomedical Engineering and Orthopedic Surgery, have been pursuing experiments that seek to catalyze stem cells to grow into, for example, bone and cartilage cells, instead of fat, smooth muscle and other cell types.

Beyond tissue engineering, the scientists believe that their technology could be used to starve a tumor by blocking growth of blood vessels that carry nutrition to a malignancy. Or the siRNA could bring on cancer cell death by interfering with other cellular processes.

siRNA is a short section of double-stranded RNA that inhibits gene expression. The molecule can jam up the machinery that produces specific proteins important to cell processes.

A current challenge to using siRNA to block growth of cancerous tumors or guide cell behavior in tissue engineering, is that the tiny material rapidly disperses when injected in the bloodstream or directly into target tissues.

Alsberg, Khanh Nguyen, a postdoctoral researcher, and Phuong N Dang a doctoral student here, packaged siRNA in a mix of polymeric materials. Under ultraviolet light, the mix is induced to form hydrogels connected by a network of polymer threads.

As the threads of the hydrogels break down, the siRNA molecules are cut loose to redirect the fate of the targeted cells. Ultimately, this system can be injected into a target tissue and application of light from outside the body will induce hydrogel formation.

"Local delivery helps target the siRNA to specific cell populations of interest, such as cancer cells in a tumor or stem cells in a bone fracture," Alsberg said. "The ability to alter cell behavior with siRNA can depend on the length of exposure time to the genetic material.

"We can tune the material properties so we can control the dose and rate at which cells are exposed to siRNA. This capacity may prove to be therapeutically valuable."

Tests showed the siRNA effectively interfered with a signal pathway of cells surrounding and inside the hydrogels over an extended period of time.

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Precise and persistent cell sabotage: Control of siRNA could aid regenerative medicine, cancer therapy

ScienceDaily (Aug. 26, 2012) A team of scientists, including faculty at the University of Massachusetts Medical School (UMMS), have discovered a gene that influences survival time in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). The study, published August 26 in Nature Medicine, describes how the loss of activity of a receptor called EphA4 substantially extends the lifespan of people with the disease. When coupled with a UMMS study published last month in Nature identifying a new ALS gene (profilin-1) that also works in conjunction with EphA4, these findings point to a new molecular pathway in neurons that is directly related to ALS susceptibility and severity.

"Taken together, these findings are particularly exciting because they suggest that suppression of EphA4 may be a new way to treat ALS," said Robert Brown, MD, DPhil, a co-author on the study and chair of neurology at UMass Medical School.

ALS is a progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually respiratory failure. The cause of most cases of ALS is not known. Approximately 10 percent of cases are inherited. Though investigators at UMMS and elsewhere have identified several genes shown to cause inherited or familial ALS, almost 50 percent of these cases have an unknown genetic cause. There are no significant treatments for the disease.

Wim Robberecht, MD, PhD, lead investigator of the Nature Medicine study and a researcher at the University of Leuven in Belgium and the Vesalius Research Center, screened for genes in zebrafish that blunt the adverse effect of the ALS mutant gene SOD1. Through this process, his team identified EphA4 as an ALS modifier. Dr. Robberecht's team went on to show that when this gene is inactivated in mice with ALS, the mice live longer.

Dr. Robberecht then turned to UMass Medical School to confirm that turning off EphA4 in human ALS cells would slow the progression of the disease. Dr. Brown and his team identified two human ALS cases with mutations in the EphA4 gene which, like the zebrafish and the mice, had unusually long survival times. This suggests that blocking EphA4 in patients with ALS may be a potential therapeutic target in the future.

In an exciting, related development, a new ALS gene (profilin-1) identified last month by UMMS scientists works in conjunction with EphA4 in neurons to control outgrowth of motor nerve terminals. In effect, gene variants at both the top and the bottom of the same signaling pathway are shown to effect ALS progression. Together these discoveries highlight a new molecular pathway in neurons that is directly related to ALS susceptibility and severity and suggests that other components of the pathway may be implicated in ALS.

"It is exciting that these two studies identify the same pathway in ALS," said John Landers, PhD, associate professor of neurology and lead author of the PFN1 study. "Hopefully this discovery will accelerate efforts to finding a treatment for ALS."

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Scientists identify new gene that influences survival in amyotrophic lateral sclerosis

Public release date: 26-Aug-2012 [ | E-mail | Share ]

Contact: Jim Fessenden james.fessenden@umassmed.edu 508-856-2000 University of Massachusetts Medical School

WORCESTER, MA A team of scientists, including faculty at the University of Massachusetts Medical School (UMMS), have discovered a gene that influences survival time in amyotrophic lateral sclerosis (ALS, also known as Lou Gehrig's disease). The study, published today in Nature Medicine, describes how the loss of activity of a receptor called EphA4 substantially extends the lifespan of people with the disease. When coupled with a UMMS study published last month in Nature identifying a new ALS gene (profilin-1) that also works in conjunction with EphA4, these findings point to a new molecular pathway in neurons that is directly related to ALS susceptibility and severity.

"Taken together, these findings are particularly exciting because they suggest that suppression of EphA4 may be a new way to treat ALS," said Robert Brown, MD, DPhil, a co-author on the study and chair of neurology at UMass Medical School.

ALS is a progressive, neurodegenerative disorder affecting the motor neurons in the central nervous system. As motor neurons die, the brain's ability to send signals to the body's muscles is compromised. This leads to loss of voluntary muscle movement, paralysis and eventually respiratory failure. The cause of most cases of ALS is not known. Approximately 10 percent of cases are inherited. Though investigators at UMMS and elsewhere have identified several genes shown to cause inherited or familial ALS, almost 50 percent of these cases have an unknown genetic cause. There are no significant treatments for the disease.

Wim Robberecht, MD, PhD, lead investigator of the Nature Medicine study and a researcher at the University of Leuven in Belgium and the Vesalius Research Center, screened for genes in zebrafish that blunt the adverse effect of the ALS mutant gene SOD1. Through this process, his team identified EphA4 as an ALS modifier. Dr. Robberecht's team went on to show that when this gene is inactivated in mice with ALS, the mice live longer.

Dr. Robberecht then turned to UMass Medical School to confirm that turning off EphA4 in human ALS cells would slow the progression of the disease. Dr. Brown and his team identified two human ALS cases with mutations in the EphA4 gene which, like the zebrafish and the mice, had unusually long survival times. This suggests that blocking EphA4 in patients with ALS may be a potential therapeutic target in the future.

In an exciting, related development, a new ALS gene (profilin-1) identified last month by UMMS scientists works in conjunction with EphA4 in neurons to control outgrowth of motor nerve terminals. In effect, gene variants at both the top and the bottom of the same signaling pathway are shown to effect ALS progression. Together these discoveries highlight a new molecular pathway in neurons that is directly related to ALS susceptibility and severity and suggests that other components of the pathway may be implicated in ALS.

"It is exciting that these two studies identify the same pathway in ALS," said John Landers, PhD, associate professor of neurology and lead author of the PFN1 study. "Hopefully this discovery will accelerate efforts to finding a treatment for ALS."

###

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Scientists identify new gene that influences survival in ALS

ScienceDaily (Aug. 26, 2012) Two opposing teams battle it out to regulate gene expression on the DNA playing field. One, the activators, keeps DNA open to enzymes that transcribe DNA into RNA. Their repressor opponents antagonize that effort by twisting DNA into an inaccessible coil around histone proteins, an amalgam called chromatin, effectively blocking access to DNA by enzymes that elongate an RNA strand.

Both teams maneuver by chemically modifying histones -- the activators by decorating histones with acetyl groups -- let's call them green flags -- causing them to loosen their grip on DNA. The repressors retaliate by marking histones with red flags, often methyl groups, which call in de-acetylase enzymes to clip off the green flags, restore the chromatin barrier and end that round of gene expression. Disturbing this biochemical balance lies at the heart of many diseases, particularly cancer.

Recently, the lab of Jerry Workman, Ph.D., investigator at the Stowers Institute for Medical Research, reported in the journal Nature that a reserve of "pre-acetylated" histones sits on the chromatin sidelines ready to sub for histones whose green flags get clipped by repressors, a tactic aiding the activators called "histone exchange." In a companion study published in the Aug. 26, 2012 Advance Online Publication of Nature Structural & Molecular Biology the Workman lab now shows that a repressor called Set2 in yeast recruits a protein assistant to block the histone exchange. That study reveals a heretofore unknown mechanism to keep gene activation under control and ensure that erroneous transcription does not occur.

"Accurate gene expression is critical for normal cell function, and when this control is lost cells grow abnormally," says Workman. "These two studies identify mechanisms used by cells to regulate gene expression, which is important for our understanding of what goes wrong in diseases marked by unregulated cell growth, like cancer."

The study began when the group, in collaboration with Stowers proteomics experts Michael Washburn, Ph.D., and Laurence Florens, Ph.D., applied mass spectrometry analysis to identify any protein expressed in yeast Saccharomyces cerevisiae that bound to chromatin in regions patrolled by Set2. Those regions were readily apparent by the presence of Set2's red flag methyl group planted in a specific histone protein interacting with DNA.

"We knew that Set2 added this mark in the middle and downstream parts of genes to recruit de-acetylases," says the study's lead author Michaela Smolle, Ph.D., a postdoctoral researcher in the Workman lab. "But the proteomic search allowed us to cast a wide net for other proteins associated with that mark -- a bit like fishing."

Among the fish caught was a component of a yeast chromatin "remodeler" known as Isw1, providing circumstantial evidence that the Set2 red flag attracts Isw1 as well as de-acetylases. Additional genomic experiments evaluating the entire genome of a yeast mutant lacking Set2 supported that idea: not only were the red methyl flags missing but the chromatin landscape was devoid of Isw1 as well.

To assess Isw1's biological function the group exploited yet another yeast mutant, this one lacking the ISW1 gene itself. Microarray analysis of global transcription in ISW1 CHD1 mutants showed widely perturbed gene expression marked by aberrant expression of RNA snippets rather than complete transcripts. Biologists view the presence of such "cryptic transcripts" as indicators of cellular stress.

Analysis of acetylation and methylation patterns in chromatin of ISW1 mutants revealed the probable cause: mutants showed ramped up histone exchange activity marked by excessive levels green-flagged pre-acetylated histones along the length of many genes, a condition likely favoring initiation of truncated RNAs.

"Our work shows that the Set2 methylation mark plays two important roles to ensure that RNA transcription starts only at the beginning of the gene and not in the middle," says Workman. "On one hand, it recruits Isw1 to block incoming histones, and on the other it also recruits a deacetylase to remove any acetylation marks that might happen to have sneaked in."

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Controlling gene expression: How chromatin remodelers block a histone pass

Newswise People who carry a G instead of an A at a specific spot in the sequence of their genetic code have roughly a six-fold higher risk of developing certain types of brain tumors, according to a study by researchers at the University of California, San Francisco and Mayo Clinic.

The study was jointly led by geneticists Margaret Wrensch, PhD, and John Wiencke, PhD, professors in the Department of Neurological Surgery at UCSF, and Robert Jenkins, MD, PhD, professor of Laboratory Medicine in the Department of Laboratory Medicine and Pathology and the Division of Laboratory Genetics at the Mayo Clinic. The findings, published on August 26, 2012 in the journal Nature Genetics, could help researchers identify people at risk of developing certain subtypes of gliomas, which account for about 4,600 of the 23,000 brain cancers newly diagnosed annually in the US.This information could lead to better surveillance, diagnosis and treatment.

Based on their findings, the scientists already are starting to think about clinical tests that could tell patients with abnormal brain scans what kind of tumor they have, by simply testing their blood.

Researchers still need to understand how the specific DNA change actually causes the tumors, said Wrensch, since this is among the first examples that a change in a non-coding portion of DNA can be so strongly associated with cancer risk.

The study began a few years ago when researchers started hunting for regions of the genome that might be associated with glioma development. They observed that a portion of chromosome 8 contained single nucleotide polymorphisms, or SNPs, that were associated with brain tumors. Then, Wrensch, Wiencke, Jenkins and their colleagues used a combination of sophisticated genomic techniques to search for the SNP that was causing brain tumors to form.

They honed in on seven candidates, including the SNP called rs55705857, which confers a relative risk for glioma approaching that seen with changes in BRCA1 for breast cancer.

Interestingly, this region was only found through the most laborious method used by the researchers next generation sequencing suggesting that experimental and mathematical shortcuts may miss such rare, highly potent gene variants, the authors say.

Wrensch and Jenkins found that having the G, or guanine, version of this SNP rather than the more common A adenine version was strongly associated with slower growing gliomas.

Understanding how this variant causes people to get these less aggressive, but still lethal, tumors will be extremely important, Wrensch said. It may eventually lead to methods to reverse the course of these tumors or possibly to prevent their formation.

As part of their work, the researchers compared the sequence of the gene variant throughout mammalian evolution and found that it has been conserved as far back as the platypus. Computer modeling indicated that the region may be a microRNA, a special kind of nucleic acid that controls the activity of genetic messages within cells. The modeling places the SNP within the functional part of the microRNA, suggesting that a change in genetic code from an A to a G could have significant consequences. The research team is investigating whether the microRNA actually exists, and what its functional implications might be.

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UCSF, Mayo Team Discovers Genomic Variant That Increases Risk of Some Brain Tumors

Geneticists soon will be able to identify an unborn childs risk of developing chronic diseases later in life and possibly shed light on other traits, such as athletic ability and intelligence, medical experts say.

The source of such information probably will be the expectant mothers blood sample. For the first time, researchers recently extracted fetal DNA from a pregnant womans blood and examined the unborn babys genome.

The procedure prenatal whole genome sequencing is not yet available in the clinical setting. But some health professionals expect that pediatricians and family doctors soon will be sifting through sequencing results of infants and older children.

Key goals of the procedure are improving detection of serious genetic disorders before a child is born and helping create preventive care plans for conditions that young patients are at risk of developing as they age.

My instinct is this will be available certainly in the next decade, and probably sooner, said Benjamin E. Berkman, MPH, deputy director of the Bioethics Core at the National Human Genome Research Institute in Bethesda, Md.

But the medical community is not prepared to address the clinical challenges and ethical issues that probably will accompany the procedure, say some bioethicists and geneticists.

Such concerns could include physician uncertainty about which results to give to families and a potential rise in abortions due to parents worries about the comprehensive genetic findings, said an article in the July-August issue of The Hastings Center Report, a bioethics journal. Berkman is a senior author of the article.

The report calls for professional medical organizations to begin educating physician members about prenatal whole genome sequencing and how to discuss the procedure with expectant couples. Although the sequencing probably will be ordered by obstetrician-gynecologists, some patients might ask their primary care physicians about the procedure, health professionals say.

The report encourages the medical community to offer guidance on the types of genetic findings physicians should offer expectant parents. It also urges scientists to conduct more research into the kinds of information parents find relevant to reproductive decision-making and how health care systems should accommodate adoption of prenatal whole genome sequencing.

The tests are here, said New York geneticist Robert W. Marion, MD. Technology is going to advance, and the public is going to learn about this. The medical community cant sit back and wait for this to happen. We have to be very aggressive in getting the word out and training doctors in the significance of this procedure. Dr. Marion is chief of the divisions of genetics and developmental medicine in the Dept. of Pediatrics at the Childrens Hospital at Montefiore and the Albert Einstein College of Medicine in New York.

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Prenatal genome sequencing expected to pose challenges to doctors

Dr. Robert C. Green, an associate professor of medicine at Harvard, sees practical as well as ethical issues in trying to warn anonymous study subjects of disease risks. (Gretchen Ertl, The New York Times)

Dr. Arul Chinnaiyan stared at a printout of gene sequences from a man with cancer, a subject in one of his studies. There, along with the man's cancer genes, was something unexpected genes of the virus that causes AIDS.

It could have been a sign that the man was infected with HIV; the only way to tell was further testing. But Chinnaiyan, who leads the Center for Translational Pathology at the University of Michigan, was not able to suggest that to the patient, who had donated his cells on the condition that he remain anonymous.

Around the world, genetic researchers using tools that are ever more sophisticated to peer into the DNA of cells are finding things they were not looking for, including information that could make a big difference to an anonymous donor.

The question of how, when and whether to return genetic results to study subjects or their families "is one of the thorniest current challenges in clinical research," said Dr. Francis Collins, the director of the National Institutes of Health.

The federal government has made the issue a priority, spending millions of dollars on research on questions unique to this new genomics era.

Researchers are divided on what counts as an important finding. Some say it has to suggest prevention or treatment. Others say it can suggest a clinical trial or an experimental drug. Then there is the question of what to do if the genetic findings only sometimes lead to bad outcomes and there is nothing to do to prevent them.

"If you are a Ph.D. in a lab in Oklahoma and think you made a discovery using a sample from 15 years ago from a subject in California, what exactly are you supposed to do with that?" asked Dr. Robert C. Green, an associate professor of medicine at Harvard.

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Genetic researchers face ethical dilemna with surprise findings

Public release date: 26-Aug-2012 [ | E-mail | Share ]

Contact: Julie Robert julie.robert@muhc.mcgill.ca 514-934-1934 x71381 McGill University Health Centre

This release is available in French.

Vitamin B12 is essential to human health. However, some people have inherited conditions that leave them unable to process vitamin B12. As a result they are prone to serious health problems, including developmental delay, psychosis, stroke and dementia. An international research team recently discovered a new genetic disease related to vitamin B12 deficiency by identifying a gene that is vital to the transport of vitamin into the cells of the body. This discovery will help doctors better diagnose this rare genetic disorder and open the door to new treatments. The findings are published in the journal Nature Genetics.

"We found that a second transport protein was involved in the uptake of the vitamin into the cells, thus providing evidence of another cause of hereditary vitamin B12 deficiency", said Dr. David Rosenblatt, one of the study's co-authors, scientist in medical genetics and genomics at the Research Institute of the McGill University Health Centre (RI MUHC) and Dodd Q. Chu and Family Chair in Medical Genetics and the Chair of the Department of Human Genetics at McGill University. "It is also the first description of a new genetic disease associated with how vitamin B12 is handled by the body".

These results build on previous research by the same team from the RI MUHC and McGill University, with their colleagues in Switzerland, Germany and the United States. In previous work, the researchers discovered that vitamin B12 enters our cells with help from of a specific transport protein. In this study, they were working independently with two patients showing symptoms of the cblF gene defect of vitamin B12 metabolism but without an actual defect in this gene. Their work led to the discovery of a new gene, ABCD4, associated with the transport of B12 and responsible for a new disease called cblJ combined homocystinuria and methylmalonic aciduria (cblJ-Hcy-MMA).

Using next generation sequencing of the patients' genetic information, the scientists identified two mutations in the same ABCD4 gene, in both patients. "We were also able to compensate for the genetic mutation by adding an intact ABCD4 protein to the patients' cells, thus allowing the vitamin to be properly integrated into the cells," explained Dr. Matthias Baumgartner, senior author of the study and a Professor of metabolic diseases at Zurich's University Children's Hospital.

Vitamin B12, or cobalamin, is essential for healthy functioning of the human nervous system and red blood cell synthesis. Unable to produce the vitamin itself, the human body has to obtain it from animal-based foods such as milk products, eggs, red meat, chicken, fish, and shellfish or vitamin supplements. Vitamin B12 is not found in vegetables.

"This discovery will lead to the early diagnosis of this serious genetic disorder and has given us new paths to explore treatment options. It also helps explain how vitamin B12 functions in the body, even for those without the disorder," said Dr. Rosenblatt who is the director of one of only two referral laboratories in the world for patients suspected of having this genetic inability to absorb vitamin B12. Dr. Rosenblatt points out that the study of patients with rare diseases is essential to the advancement of our knowledge of human biology.

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Vitamin B12 deficiency: Tracking the genetic causes

26 August 2012 Last updated at 19:58 ET

A centre for research into genetics at Edinburgh University is to benefit from almost 60m of funding.

The money, from the Medical Research Council, will help scientists gain fresh insights into conditions such as cancer, arthritis, and schizophrenia.

The grants could also help doctors develop and deliver new tests and therapies for patients.

Edinburgh University said its Institute of Genetics and Molecular Medicine is already one of the largest in Europe.

The funding - paid over the next five years - aims to consolidate the IGMM's position as a world leader in genetics research.

Institute director, Prof Nick Hastie said: "The challenge we face is to work out how human genes work together to build a human.

"We also want to find out how subtle DNA differences help shape human diversity and influence susceptibility to a wide range of common diseases. This funding will help us to turn the potential of the genetic revolution into reality."

The money has been awarded to teams carrying out research on schizophrenia, cystic fibrosis, cancer, osteoarthritis and genetic eye disorders, amongst other conditions.

The IGMM is a partnership between the Medical Research Council, the University of Edinburgh's Centre for Molecular Medicine and Cancer Research UK.

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Funding boost for genetics centre

Phosphorus Starvation Tolerance (PSTOL1) gene helps rice plants produce around 20 percent more grain. Credit: IRRI

In a discovery that could help boost food output across the globe, scientists have discovered a new gene that enables rice plants to produce more grain.

An international team of scientists has found the gene, Phosphorus Starvation Tolerance (PSTOL1), which helps rice plants produce around 20 percent more grain by increasing the uptake of phosphorus, a key plant nutrient. The gene helps rice grow a longer and better root system enabling it to gain access to more phosphorus.

"For many years we have searched for genes that improve phosphorus uptake," saidDr Sigrid Heuer, senior scientist at theInternational Rice Research Institute(IRRI).

Usually, farmers apply phosphorus fertilisers to increase productivity but on problem soils phosphorus often gets locked in the soil making it unavailable to plants. Now scientists have found the gene that helps grow rice plants even in low phosphorus soil. A study conducted on rice plants in Indonesia and the Philippines found that the PSTOL1 gene helps produce more grain evenin soil that has low phosphorus.

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During the experiment, scientists bred the rice with the PSTOL gene. The plants are not genetically modified but just bred using smart modern breeding techniques. Then they planted the rice in soil that is very low in phosphorus.

The study found that the rice bred with PSTOL gene produced about 20 percent more grain than rice without the gene.

ThePSTOL1gene is also being tested in rice varieties for more productive irrigated rice-growing areas and initial results show that the plants grow a better root system and yield higher production too. This means it could help farmers in these areas reduce their fertiliser use and expenditure without compromising productivity, according to a Eurekalert report.

Globally, more than 43.3 million tons of rice is produced. Despite this, an estimated five million children die due to starvation across the globe. The present discovery is expected to increase rice output significantly and fight hunger.

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Gene That Can Boost Rice Output Discovered by Scientists

Race is everywhere in medicine. Mosthealth statistics are broken down by race. We routinely characterize diseases by which populations they affect more and less and medications by which ethnicities respond better or worse.

Its so ubiquitous that its easy to take for granted as justified. But the use of race in medicine is a subject that is vigorously debated. Whenever a new study comes out stratifying results by race, there are inevitably supporters and critics.

The question under debate: is there a place for race in medicine?

Theres a growing number who say we should toss this way of thinking entirely. Many scholars now contend that race is closer to a social construct than a biological category, and theres the legitimate fear that pointing out differences between races sends the message that the difference is biological. Even if there are certain genetic differences among populations, we know that self-reported race is at best a crude proxy for indicating them. Moreover, studies often do not adjust for all other variables besides genetics, such as socioeconomic status, culture, and discrimination meaning if differences are shown, the knee-jerk tendency to think biology might overshadow important environmental disparities that deserve our attention. There are social concerns too, in that historically ethnicity in research has been abused by pseudoscientists with racist agendas of demonstrating the superiority of certain people over others. In light of that history, profound sensitivity toward using race as a variable in medicine is understandable and warranted.

Part of the problem may be that some simply do not give it enough thought. There are some who stratify any data they collect on any health-related subject by race because thats what others did before them, along with others before that. But when you do any data analysis, you need to justify its being done. Theres no such thing as just laying out the facts because there is no such thing as a predetermined set of facts that we either expose or hide. We make choices with everything. Collecting, breaking down, and representing data all involve choices. When comparing groups, we can draw the lines wherever we want. Telling of this point is that many studies that talk about race still only compare blacks to whites, ignoring all other groups along with cases of mixed ancestry.

When the choice lies with the researcher, she has an obligation to use it responsibly. As such, its not enough to enough to justify a project with some ambiguous version of: this will contribute to the literature by showing something we do not know. We dont know infinite numbers of things. Research has to have value. At the forefront of every decision should be the questions: Whats the point? Are the differences Im trying to show relevant to anything? Are there implications for disease prevention, diagnosis, management, or treatment?

Sometimes, indeed the answer is yes. There have been cases where thinking about race, even as a rough guide, have led to benefits for patients. Knowing that sickle cell anemia is more prevalent among populations of sub-Saharan African ancestry can tip physicians off for earlier and thereby more effective diagnosis and management. Since Tay-Sachs is a genetic disease with increased prevalence among Ashkenazi Jews, Jewish communities early on welcomed genetic testing for prospective parents and by doing so dramatically reduced the incidence of the disease. Individuals of Asian descent are more likely to carry certain genetic polymorphisms resulting in slower drug metabolism meaning patients need lower doses to achieve the desired effects and avoid toxicity. There are many more examples. While it is such an important point that Ill say it again that race is only a very imperfect proxy for genetics there has been demonstrated medical value in being aware of these trends.

The reason is that medicine is a field that uses heuristics simple rules of thumb that help home in on best guesses when comprehensive searches are not feasible. These shortcuts are so frequently employed because medicine is the perfect storm of information overload combined with limited time. Best guesses in medicine are probabilistic; doctors collect clues from various sources to select more likely and less likely options. Every test, every new piece of information contributes to that ranking. Thus, some argue that just as doctors clue into best guesses based on a patients constellation of symptoms and test results, so too can race be used as an approximate guide. With the recognition that heuristics can lead to biases, the solution is not to discard them but rather to make doctors more cognizant of biases so they can work to eliminate them and use heuristics more effectively.

The use of race in medicine is a deeply sensitive issue and should be treated as such. One thing to note is that in contrast to shameful periods in history that focused on race with unethical agendas, the vast majority of current research is completely well-intentioned, toward the goal of optimally tailoring medical care to a diverse patient population. Those on both extremes of the debate are looking out for patients. So where does that leave us? While there is a place for race in medicine, the literature also remains rife with studies with seem to point out differences with no valid reason for pointing out differences, and my sense is that theres a greater tendency to overuse race when its not appropriate than to neglect it when it is. The burden should be on every medical researcher who wants to talk about race to be explicit as to what contribution this data would make to the world. And, if those measures fail, it would behoove readers and patients to apply just as critical an eye.

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When should medicine talk about race?

Otago University Genetics Lecture 'Outdated' and Likely to Mislead

The University of Otago is being challenged to put caveats on claims made in its Genetics lectures, that international consumer concern over Genetically Modified food can be ignored.

The lectures based onresearch over ten years, claim our overseas customers won't care about GE in our food exports, and that there is no risk to Brand New Zealand from Genetically Engineered foods.One study also shows nuclear power stations, and intensive feed-lots are fine for our Brand and international reputation.

However, the claims are based on research that with hindsight is clearly flawed.

Work bya team led by Otago University Marketing lecturer Associate Professor John Knight, included running food stalls in different countries to test consumer acceptance of GE food, and interviewing first-time tourists on arrival in Auckland.

Much of the research was based on the assumption that a key consumer benefit would be that GE food will have fewer toxic chemical sprays than conventional crops. But data on chemical exposure are showing this to be the least likely outcome from GE foods over the past decade.

Another assumption was that consumer concerns for food safety were unfounded, and the result of media hype and scaremongering. The fact that Food Authorities had approved these foods as safe was taken as doctrine. Today scientists are warning of serious risks evidenced in peer-reviewed studies.

"These basic assumptions are now highly doubtful, which means the data is unreliable and could likely mislead decision-makers,"says Jon Carapiet, spokesman for GE-Free NZ in food and environment.

"The rosy picture painted that consumers don't mind GE is based on incomplete knowledge on the part of the consumer to make a reasonable judgement."

The research is also totally blind to Brand marketing:promoting New Zealand products as GE-free and meeting the highest organic standards for purity in the world, both of which fit our values and clean green image.

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Otago Uni Genetics Lecture Outdated and Likely to Mislead

NEW YORK (GenomeWeb News) The National Institute of Environmental Health Sciences plans to provide up to $3 million next year to fund research into how exposure to toxic chemicals in the environment affects gene expression.

In a new funding announcement, NIEHS said that it plans to fund grants with up to $400,000 next year that seek to define how environmental exposures affect proteins and other elements that govern gene expression patterns and chromatin states.

Exposure to toxicants that cause changes in gene expression and DNA methylation profiles can lead to diseases such as autoimmune and neurodevelopmental disorders and cancer. NIEHS has over the past decade been supporting projects that focus on exposures to toxicants such as arsenic, tobacco smoke, airborne particulates, and others.

The institute said it has already made "a significant investment" in research to identify epigenetic signatures of exposure, and now it wants to support studies that home in on how these exposures perturb proteins and processes that occur upstream of DNA methylation and other epigenetic marks.

The goal for this program is to begin to move beyond descriptive and correlative studies to understand the mechanisms involved in environmental exposure and gene expression.

Projects funded under this program may include, but are not limited to, research into chromatin accessibility and nucleosome positioning; the role of exposures in influencing the distribution, turnover, and positioning of nucleosomes; chromatin remodeling; the effects of exposures on non-coding RNA DNA/nucleosome binding; and studies that examine mechanisms involved in exposure related to the disruption of normal cis-regulatory functions.

Also under this funding program, the National Institute on Drug Abuse plans to fund one award of $400,000 for research that investigates the impact of drugs of abuse on chromatin. These projects will use high-throughput assays that can reveal changes in chromatin looping, 3D-chromatin structure, or interactions between non-coding RNAs with chromatin to study impacts of drugs such as nicotine, stimulants, opioids, abused prescription medicines, psychedelics, and others.

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NIEHS to Fund Studies of Toxic Exposure Impacts on Gene Expression, Chromatin

A humble soil bacteria has become a genetically engineered factory capable of making fuel for cars. But the project still has to get out of the lab and scale up to industrial-size production.

The MIT project aims to make transportation fuels 10 times more efficiently than existing biofuels derived from living organisms. Researchers swapped out the genes of the R. eutropha bacterium so that it can create isobutanol an alcohol that can replace or blend with gasoline used by vehicles.

"We've shown that, in continuous culture, we can get substantial amounts of isobutanol," said Christopher Brigham, a biologist at MIT.

Many similar projects use microbes that make the biofuels within their bodies, so that researchers must kill the microbes to get the fuel out. But the MIT effort has succeeded in making the bacteria spit gasoline out into the surrounding liquid medium for easy harvesting.

The natural bacteria usually stores carbon by creating carbon polymers similar to petroleum-based plastics. Brigham and his colleagues Jingnan Lu, Claudia Gai and Anthony Sinskey managed to remove several genes while adding another organism's gene so that the bacteria made isobutanol rather than the carbon polymer.

For their next trick, the MIT researchers hope the genetically engineered bacteria could eventually transform carbon dioxide into fuel a way of using up the greenhouse gas that contributes heavily to global warming. The bacteria already naturally use hydrogen and carbon dioxide for growing.

Additional modifications could allow the bacteria to use carbon from sources such as agricultural field waste or city waste. The research received about $1.8 million from ARPA-E, the U.S. Department of Energy's research arm for high-risk, high-reward projects, from July 2010 until July 2013.

The MIT research is detailed in the August issue of the journal Applied Microbiology and Biotechnology.

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Genetic Engineering Has Turned Bacteria Into Fuel For Cars

NEW YORK, NY--(Marketwire -08/24/12)- A new shift in thinking about genetics could transform cancer treatment over the next five years, according to Kalorama Information. The healthcare market research publisher says therapies such as monoclonal antibodies may have competition from an unexpected source: changes in the genetic material that occur for reasons other than DNA base pair alteration. The finding was made in its recent report, "Epigenomics, Present and Future Applications for Pharmaceuticals and Diagnostics."

Epigenomics constitutes a challenge to the long-held paradigm of DNA base pair sequences as the prime determinant of the phenotype. Examples of such changes include DNA methylation and histone acetylation, both of which have been known for many years to cause changes in gene expression. The report says that drugs that target the epigenome offer a number of important advantages over other forms of cancer treatment; most notably they can be taken orally, saving the patient discomfort, cost and inconvenience. They are also more focused specifically against their target.

"Rather than blasting away machine gun style at the malignancy, they aim at a very specific reaction site within the cell," said K. John Morrow, Jr., PhD, Kalorama analyst and author of the report. "So far their side effects have proven to be relatively minor."

The report says that while epigenomic therapeutics have been around for a while, a raft of new clinical trials are in progress, and with any luck the next few years will see a number of FDA approvals for these agents. There are already FDA-approved epigenetic anti-cancer drugs available, such as azacytidine, and trials are underway that combine a non-epigenetically-based drug with one of the compounds under evaluation.

Perhaps the only concern to companies wishing to pursue the Kalorama recommendation is the competition, the fact that so many of the major pharmaceutical and biotech players are already building vigorous epigenomics programs. These programs include investigations into epigenomic mechanisms that engage cardiovascular disease and neurological dysfunction. Some may see these as non-cancer-related but they are. It is known that flexible epigenomic parameters exist that can change gene expression under external influences, while endowed with the ability to stably propagate these modifications from one generation to the next.

"At present the major pharmaceutical companies are faced with a downward spiral of profitability," Morrow said. "Epigenomic technologies represent an escape from this corrosive cycle of greater and greater R&D expenditures and poorer and poorer yields of FDA-approved pharmaceuticals."

Kalorama Information's report, "Epigenomics, Present and Future Applications for Pharmaceuticals and Diagnostics," has an extensive survey of information on market forecasts and company activities in the marketplace.

About Kalorama InformationKalorama Information, a division of MarketResearch.com, supplies the latest in independent medical market research in diagnostics, biotech, pharmaceuticals, medical devices and healthcare; as well as a full range of custom research services. We routinely assist the media with healthcare topics. Follow us on Twitter, LinkedIn and our blog.

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Highly-Targeted Epigenomic Treatments May Change Cancer Therapy

SILVER SPRING, Md. and SINGAPORE, Singapore, Aug. 24, 2012 (GLOBE NEWSWIRE) -- Nuvilex, Inc. (OTCQB:NVLX), an international biotechnology provider of cell and gene therapy solutions, announced today that Dr. Robert F. Ryan, President and CEO of Nuvilex, is in Asia and Singapore this week for numerous meetings with the Executives and staff of its wholly-owned subsidiary, Austrianova Singapore (ASPL), as well as other companies and groups in the region.

In addition to specific work with Dr. Walter Gunzburg, ASPL Chairman, and Dr. Brian Salmons, President and CEO of ASPL, and the other ASPL executives and staff regarding Nuvilex's pancreatic cancer treatment, other avenues for the development of Nuvilex and its Cell-in-a-Box(R) live cell encapsulation technology have been discussed.

Since his arrival Tuesday, management has been working closely together discussing possible partnerships with other entities regarding the use of the cell encapsulation technology, a major combined effort for the company. Meetings in Beijing and Singapore have included discussions with previous partners of ASPL regarding potential business opportunities.

In commenting upon his effort in Singapore, Dr. Ryan stated, "These meetings, especially those with the staff of the recently-acquired subsidiary, Austrianova Singapore, have been both timely and crucial as Nuvilex progresses in the biotechnology arena. It's important to establish and solidify the link between our two companies and staff and to ensure a seamless integration of ASPL into Nuvilex for the benefit of all of our staff and future. This is turning out to be a fantastic experience and I believe much will be gained from my visit."

About Nuvilex

Nuvilex, Inc. (OTCQB:NVLX) is an international biotechnology provider of live therapeutically valuable, encapsulated cells and services for research and medicine. A great deal of work is ongoing to move Nuvilex and our Austrianova Singapore subsidiary forward. More information is anticipated to be coming regarding Dr. Ryan's ongoing travel for the Company. Our company's clinical offerings will include cancer, diabetes and other treatments using the company's cell and gene therapy expertise and live-cell encapsulation technology.

The Nuvilex, Inc. logo is available at http://www.globenewswire.com/newsroom/prs/?pkgid=13494

Safe Harbor Statement

This press release contains forward-looking statements described within the 1995 Private Securities Litigation Reform Act involving risks and uncertainties including product demand, market competition, and meeting current or future plans which may cause actual results, events, and performances, expressed or implied, to vary and/or differ from those contemplated or predicted. Investors should study and understand all risks before making an investment decision. Readers are recommended not to place undue reliance on forward-looking statements or information. Nuvilex is not obliged to publicly release revisions to any forward-looking statement, reflect events or circumstances afterward, or disclose unanticipated occurrences, except as required under applicable laws.

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Nuvilex's President and CEO in Singapore for Meetings With Its Subsidiary Austrianova Singapore

Public release date: 24-Aug-2012 [ | E-mail | Share ]

Contact: Kim Polacek kim.polacek@moffitt.org 813-745-7408 H. Lee Moffitt Cancer Center & Research Institute

Researchers at Moffitt Cancer Center and colleagues have identified PHF20, a novel transcriptional factor, and clarified its role in maintaining the stability and transcription of p53, a gene that allows for both normal cell growth and tumor suppression. PHF20, the researchers found, plays a previously unknown and unique role in regulating p53.

When p53 is activated, it can mend DNA damage and eliminate cancer cells by binding to DNA. How p53 maintains its basal level and becomes activated remain elusive, but identifying transcription factor PHF20 and understanding its interaction with p53 and its induction of p53 protein stability and transcription has provided a clue.

Results of their research appeared in a recent issue of Nature Structural & Molecular Biology and also in The Journal of Biological Chemistry.

"When a cell undergoes alterations that predispose it to become cancerous, p53 is activated to either mend the DNA damage or eliminate the affected cells, thereby preventing the development of tumors," said Jin Q. Cheng, Ph.D., M.D., a senior member of the Molecular Oncology Department and Molecular Oncology and Drug Discovery Program at Moffitt. "A number of mechanisms normally keep a regulatory strong check on p53 and allow for rapid activation. Still much is unknown about the mechanism of p53 regulation."

After identifying PHF20 as a novel transcriptional factor, the researchers set out in subsequent studies to probe the function of human PHF20 and its effect on p53. They found that PHF20 not only transcriptionally induces p53 but also directly interacts with and stabilizes p53. Akt negatively regulates these processes by interaction and phosphorylation of PHF20.

To determine whether the absence of PHF20 might regulate stress-induced p53 expression, the researchers "knocked down" PHF20. In doing so, they demonstrated that in the absence of PHF20, p53 was reduced. These findings established the role of PHF20 as a key regulator of p53 and additional link between Akt and p53.

According to Cheng, the identification of PHF20 as a regulator of p53 is significant because PHF20 "participates in simultaneous multiple interactions with other proteins and DNA" and serves to stabilize and induce p53.

"Regulation of p53 is critical to allow both normal cell growth and tumor suppression," explained Cheng. "However, further investigation is required to understand PHF20 tumor suppressor function and its possible involvement in human malignancy."

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Moffitt Cancer Center researchers and colleagues identify PHF20, a regulator of gene P53

August 23, 2012

Brett Smith for redOrbit.com Your Universe Online

In a discovery that could have major implications for the worldwide food supply, scientists at the International Rice Research Institute (IRRI) in the Philippines have identified and leveraged a gene that allows rice to thrive in nutrient deficient soil.

According to their report published this week in the journal Nature, the researchers were able to improve test yields of rice planted in the Philippines, Japan, and Indonesia by 20 percent.

We found a gene that enhances phosphorus uptake in low phosphorus conditions. We have been looking for it for many years, said lead author Sigrid Heuer.

The gene, phosphorus-starvation tolerance 1 (PSTOL1), was first identified in the Kasalath rice variety that is native to India and grows well in soils low in phosphorus. About a decade ago, scientists identified one or more genes in the plant that allowed it to grow successfully in these scarce conditions. Because of the complexity of the genetic mechanism that imparts this unique ability to the Kasalath plants, it took the IRRI team three years to identify the specific gene responsible.

Heuer and his team were able to isolate and breed the gene through cross-pollination, an important distinction for those against using genetic engineering techniques on food products. Advocates of genetic technology say using traditional pollination techniques can translate into years or even decades of testing before a new strain reaches the market.

The PSTOL-1 gene enables developing rice plants by maximizing their roots extraction of phosphorus from the soil. Successful breeding to the gene would reduce the dependence on phosphorus-rich fertilizer in poorer sections of Asia that are known to have nutrient deficient soil.

Because many plant roots are only able to extract a tiny amount of phosphorus from the soil, farmers around the world spread phosphorus-based fertilizer on their fields. In poorer countries, this solution is often too costly, resulting in less than optimal yields when the plants mature. In wealthier countries, more robust rice plants would need less fertilizer, meaning lower costs and less damaging phosphate runoff into the water table.

Fifty percent of worlds arable land is too low in phosphorus. Its not like if you have this gene that the plants dont need phosphorus anymore, Heuer told Tan Ee Lyn of Reuters.

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Rice Gene Allows Crop To Thrive In Nutrient Deficient Soil

By Michelle Fay Cortez - 2012-08-23T04:01:00Z

Scientists using rapid genetic testing to track the path of a deadly bacterium in a Maryland medical center discovered unsuspected ways pathogens can spread and learned a new tool to combat hospital-acquired infections.

The DNA screening allowed staff at the National Institutes of Healths research hospital in Bethesda, Maryland, to link infections with a multidrug resistant strain of Klebsiella pneumoniae weeks after the first case was found, even though there were no obvious ties among the patients. Uncovering the way the bacteria moved silently though the hospital for weeks confirmed an outbreak was under way and prompted aggressive measures to control the pathogen that infected 18 people.

This has changed the practice of medicine in our hospital and we hope it will change the way other hospitals would control a similar outbreak, said Julie Segre, a senior investigator at the National Human Genome Research Institute.

Advances in genetic sequencing allowed researchers to map minute differences in the DNA of the bacterium in less than a week, proving all 18 cases began with a single patient in June 2011.

The first patient, a 43-year-old New York woman, was isolated as soon as she arrived at NIHs 243-bed hospital in Bethesda. Infection-control procedures, such as gloves and gowns for all staff and visitors, were used to contain the dangerous bacteria.

The effort was unsuccessful. Seventeen other patients subsequently fell ill, at an alarming rate of one a week. Eleven people died, six from K. pneumoniae and five from underlying diseases that were exacerbated by the bacteria, which evaded all commonly used antibiotics, including carbapenem, one of the most potent germ-killers.

Its an emerging pathogen, but weve never had a patient with it in our hospital or in this area that we were aware of, Segre said.

Hospital-acquired infections arent new, occurring in more than 1 million patients each year in the U.S. The mystery of the K. pneumoniae case, detailed yesterday in the journal Science Translational Medicine, arose because the second case of infection didnt emerge until three weeks after the first patient was treated and discharged. The bacteria turned up in a trachea of an immune-compromised patient, who had never been in the same hospital ward as the woman from New York.

After the first patient was released, we did routine surveillance to see if anyone in the hospital was exposed and the tests came back negative for weeks, Segre said. On August 5, we got our second patient with a Klebsiella infection. We were stunned.

Originally posted here:
Gene Detectives Find New Tool to Contain Deadly Bacteria

ScienceDaily (Aug. 23, 2012) The discovery of a 'switch' that modifies a gene known to be essential for normal heart development could explain variations in the severity of birth defects in children with DiGeorge syndrome.

Researchers from the Walter and Eliza Hall Institute made the discovery while investigating fetal development in an animal model of DiGeorge syndrome. DiGeorge syndrome affects approximately one in 4000 babies.

Dr Anne Voss and Dr Tim Thomas led the study, with colleagues from the institute's Development and Cancer division, published August 23 in the journal Developmental Cell.

Dr Voss said babies with DiGeorge syndrome have a characteristic DNA mutation on chromosome 22 (22q11 -- chromosome 22, long arm, band 11), but exhibit a range of mild to severe birth defects, including heart and aorta defects.

"The variation in symptoms is so prominent that even identical twins, with the exact same DNA sequence, can have remarkably different conditions," she said. "We hypothesised that environmental factors were probably responsible for the variation, via changes to the way in which genetic material is packaged in the chromatin," Dr Voss said.

Chromatin is the genetic material that comprises DNA and associated proteins packaged together in the cell nucleus. Chemical marks that sit on the chromatin modify it to instruct when and where to switch genes on or off, making a profound difference to normal development and cellular processes.

The research team found a protein called MOZ, the 'switch' which is involved in chromatin modification, was a key to explaining the range of defects seen in an animal model of DiGeorge syndrome. "MOZ is what we call an chromatin modifier, which means it is responsible for making marks on the chromatin that tell genes to switch on or off," Dr Voss said.

"In this study, we showed that MOZ regulates the major gene, called Tbx1, in the 22q11 deletion. Tbx1 is responsible for heart and aortic arch development. In mouse models that have no Moz gene, Tbx1 does not work properly, and the embryos have similar heart and aorta defects to those seen in children with DiGeorge syndrome. We showed that MOZ is crucial for normal activity of Tbx1, and the level of MOZ activity may contribute to determining how severe the defects are in children with DiGeorge syndrome," Dr Voss said.

Dr Voss said the study also showed that the severity of birth defects in DiGeorge syndrome could be compounded by the mother's diet, particularly if the MOZ switch is not working properly. The research team showed that reduced MOZ activity could conspire with excess retinoic acid (a type of vitamin A) to markedly increase the frequency and severity of DiGeorge syndrome.

"In our mouse model, we saw that retinoic acid exacerbated the defects seen in mice with mutations in the Moz gene. In fact, in mice that had one normal copy of MOZ and one mutated copy, the offspring look completely normal, but if the mother's diet was high in vitamin A, the offspring developed a DiGeorge-like syndrome. This suggests that MOZ, when coupled with a diet high in vitamin A (retinoic acid), may play a role in the development of DiGeorge syndrome in some cases.

Link:
Gene 'switch' may explain DiGeorge syndrome severity

The Union Cabinet has approved the proposal of Ministry of Agriculture, Department of Agricultural Research and Education for the establishment of Indian Institute of Agricultural Biotechnology at Ranchi (Jharkhand) at a cost of Rs. 287.50 crore during the 12th Five year plan.

The Indian Institute of Agricultural Biotechnology (IIAB) at Ranchi (Jharkhand) will be established as a deemed University with the following schools:

School-I School of Genomics

School-II School of Bioinformatics

School-III School of Genetic Engineering

School-IV Nano Biotechnology, Diagnostics and Prophylactics

School-V School of Basic and Social Sciences and Commercialization

The mandate of the Institute would be to undertake multi-disciplinary basic and strategic research with a view to future developing crops for traits such as increased yield, or increased tolerance to biotic and abiotic stress; to design and start academic programmes to develop the highly trained manpower required for fundamental research in agricultural biotechnology, and award post graduate doctoral and post-doctoral degrees; to provide its research output to breeders and developers in agricultural universities and other institutions, to develop the germplasm, vaccines etc. that would enhance productivity and reduce losses due to biotic and abiotic stress; act as a mother institute that would provide both curricula and course material to India`s agricultural universities and other institutions who are running or trying to establish successful agricultural biotechnology graduate and post graduate programmes.

Background:

There is growing demand for food, fodder and feed. A healthy growth in the GDP is likely to further boost domestic demand for food. About 53 per cent of the food demand escalation is expected to occur due to growth in population and the rest due to improve per capita consumption. The current production and the projected demand by the year 2020, are 245 and 284 million tonnes of food grain, 138 and 160 million tonnes of vegetables, 74 and 97 million tonnes of fruits, and 32 and 69 million tonnes of oilseeds respectively. As the net cultivable area of 142 million hectares is not likely to increase, the gain in food production will have to be met by increasing productivity. There is need, therefore, for a renewed and vigorous effort to increase productivity and production through the "Second Green Revolution".

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(RTTNews.com) - Seattle Genetics Inc. (SGEN) has initiated a phase Ib clinical trial evaluating SGN-75 in combination with everolimus for patients with advanced metastatic renal cell carcinoma or RCC. The study is designed to assess the safety and antitumor activity of SGN-75 in combination with everolimus. Seattle Genetics is a leader in the field of antibody-drug conjugates or ADCs and SGN-75 is an ADC targeted to CD70.

The study is a phase Ib, open-label, dose-escalation trial to evaluate the safety and antitumor activity of SGN-75 in combination with everolimus, an mTOR inhibitor, in patients with CD70-positive metastatic RCC. Everolimus is an oral prescription medication used to treat advanced RCC when certain other medicines, such as sunitinib or sorafenib,have not worked.

The trial is enrolling patients who have earlier been treated with one or two tyrosine kinase inhibitors or TKIs. The primary endpoint is safety, with key secondary endpoints of best clinical response, progression-free survival (PFS) and overall survival (OS). The study is expected to enroll up to 40 patients at multiple centers in the U.S.

For comments and feedback: contact editorial@rttnews.com

http://www.rttnews.com

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Seattle Genetics Begins Phase Ib Study Of SGN-75 Combined With Everolimus

BOTHELL, Wash.--(BUSINESS WIRE)--

Seattle Genetics, Inc. (SGEN) today announced the initiation of a phase Ib clinical trial evaluating SGN-75 in combination with everolimus (Afinitor) for patients with advanced metastatic renal cell carcinoma (RCC). The trial is designed to assess the safety and antitumor activity of SGN-75 in combination with everolimus. Seattle Genetics is a leader in the field of antibody-drug conjugates (ADCs) and SGN-75 is an ADC targeted to CD70.

ADCs have the potential to change the way many types of cancer are treated, and we are excited to evaluate our ADC product candidate, SGN-75, in this phase Ib trial for patients with CD70-expressing RCC, said Jonathan Drachman , M.D., Senior Vice President, Research and Translational Medicine at Seattle Genetics. We are encouraged by the preliminary single-agent activity and tolerability demonstrated by SGN-75 in RCC patients and by our preclinical data suggesting synergy between auristatin-containing ADCs and mTOR inhibitors, including everolimus. We look forward to investigating whether this combination can provide therapeutic benefit to patients who currently have limited treatment options.

The study is a phase Ib, open-label, dose-escalation clinical trial to evaluate the safety and antitumor activity of SGN-75 in combination with everolimus, an mTOR inhibitor, in patients with CD70-positive metastatic RCC. Everolimus is an oral prescription medication used to treat advanced RCC when certain other medicines, such as sunitinib or sorafenib, have not worked. The trial is enrolling patients who have previously been treated with one or two tyrosine kinase inhibitors (TKIs). The primary endpoint of the trial is safety, with key secondary endpoints of best clinical response, progression-free survival (PFS) and overall survival (OS). The study is expected to enroll up to 40 patients at multiple centers in the United States.

Despite the use of immunotherapy, tyrosine kinase inhibitors and mTOR inhibitors, many patients with kidney cancer ultimately experience progression of their disease, said Elisabeth Heath, M.D., Associate Professor of Oncology at Barbara Ann Karmanos Cancer Institute and investigator for this phase Ib clinical trial. Kidney cancer tends to resist treatments after it stops responding to initial therapy, clearly demonstrating a need to identify new treatment approaches, such as targeted therapies directed to novel targets and combination therapy.

For more information about the trial, including enrolling centers, please visit http://www.clinicaltrials.gov.

About SGN-75

SGN-75 is an ADC composed of an anti-CD70 antibody attached to a synthetic cytoxic cell-killing agent, monomethyl auristatin F (MMAF), using Seattle Genetics proprietary technology. The ADC is designed to be stable in the bloodstream, and to release its cytoxic agent upon internalization into CD70-expressing tumor cells. This approach is intended to spare non-targeted cells and thus reduce many of the toxic effects of traditional chemotherapy while enhancing the antitumor activity.

About Renal Cell Carcinoma

Renal cell carcinoma (RCC) forms in the kidney, which filters and cleans the blood. Metastatic RCC occurs when the cancer has spread to other parts of the body. RCC is the most common type of kidney cancer in adults, representing approximately 90 percent of cases. The American Cancer Society estimates that nearly 65,000 new cases of kidney cancer will be diagnosed in the United States during 2012, and approximately 13,600 people will die from the disease.

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Seattle Genetics Announces Initiation of a Phase Ib Trial of SGN-75 in Combination with Everolimus for Patients with ...

WALTHAM, Mass.--(BUSINESS WIRE)--

Interleukin Genetics, Inc. (ILIU) announced today that Lewis H. Bender has resigned as Chief Executive Officer and as a member of the Board of Directors, effective August 23, 2012, in order to pursue other business opportunities. The Board of Directors has appointed Kenneth S. Kornman, DDS, Ph.D., the Company's founder and current President and Chief Scientific Officer, as Chief Executive Officer and as a member of the Board of Directors. Dr. Kornman will also continue his duties as President and Chief Scientific Officer.

On behalf of the Board of Directors of Interleukin, I would like to thank Lew Bender for his significant contributions to Interleukins development and growth and wish him success in his new endeavors, stated James Weaver, Chairman of the Board of Directors. We are very pleased that Ken Kornman has accepted the role of Chief Executive Officer, and we look forward to his leadership of the Company.

I welcome the opportunity to lead Interleukin during this exciting time and to work with our new strategic partner, Delta Dental of Michigan, toward our goal of potentially providing more personalized care for the prevention of periodontal disease, said Ken Kornman. I also look forward to working with senior management and all Interleukin employees to achieve our collective goal of advancing all of our programs, including our weight management and osteoarthritis programs.

About Interleukin Genetics, Inc. Interleukin Genetics, Inc. (ILIU) develops and markets a line of genetic tests under the Inherent Health and PST brands.The products empower individuals to prevent certain chronic conditions and manage their existing health and wellness through genetic-based insights with actionable guidance. Interleukin Genetics leverages its research, intellectual property and genetic panel development expertise in metabolism and inflammation to facilitate the emerging personalized healthcare market. The Company markets its tests through partnerships with health and wellness companies, healthcare professionals and other distribution channels. Interleukin Genetics flagship products include its proprietary PST genetic risk panel for periodontal disease and tooth loss susceptibility sold through dentists and the Inherent Health Weight Management Genetic Test that identifies the most effective diet and exercise program for an individual based on genetics. Interleukin Genetics is headquartered in Waltham, Mass. and operates an on-site, state-of-the-art DNA testing laboratory certified under the Clinical Laboratory Improvement Amendments (CLIA). For more information, please visit http://www.ilgenetics.com.

Certain statements contained herein are forward-looking statements, including statements relating to working with Delta Dental of Michigan to potentially provide more personalized care for the prevention of periodontal disease and advancing our other current programs, including our weight management and osteoarthritis programs.Because such statements include risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Factors that could cause actual results to differ materially from those expressed or implied by such forward-looking statements include, but are not limited to, those risks and uncertainties described in the Interleukin Genetics annual report on Form 10-K for the year ended December 31, 2011 and other filings with the Securities and Exchange Commission. Interleukin Genetics disclaims any obligation or intention to update these forward-looking statements.

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Interleukin Genetics Announces Executive Management Changes

Neuropathic pain associated with diabetes, shingles, and traumatic injury affects up to 18 percent of the population and can be difficult or impossible to effectively treat. Using gene therapy, Yale neurologists have managed to repair neurons associated with traumatic nerve injury pain in rats.

Since the therapy targets only cells in the pain-sensing neurons outside the brain and spinal cord, this method can avoid some of cognitive problems associated with other pain therapies that also work on the central nervous system, said Omar Samad, research scientist in neurology and lead author of the paper published online Aug. 21 in the journal Molecular Therapy.

The work was conducted in the laboratory of Stephen Waxman, the Bridget M. Flaherty Professor of Neurology and director of the center for neuroscience and regeneration research, and it was supported by the Department of Veterans Affairs and the Nancy Taylor Foundation for Chronic Diseases.

Other authors are Andrew Tan, Xiaoyang Chen, Edmund Foster, and Sulayman Dib-Hajj.

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Research in the News: Gene therapy shows promise in neuron repair and pain relief