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Archive - May 2013

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May 13th

Rotavirus Vaccine Developed in India Demonstrates Strong Efficacy

The Government of India's Department of Biotechnology (DBT) and Bharat Biotech announced positive results from a Phase III clinical trial of a rotavirus vaccine developed and manufactured in India. Data from the trial, presented on May 14, 2013 at the International Symposium on Rotavirus Vaccines for India—The Evidence and the Promise, showed ROTAVAC® to have an excellent safety and efficacy profile. The clinical study demonstrates for the first time that the India-developed rotavirus vaccine ROTAVAC® is efficacious in preventing severe rotavirus diarrhea in low-resource settings in India. ROTAVAC® significantly reduced severe rotavirus diarrhea by more than half—56 percent during the first year of life, with protection continuing into the second year of life. Moreover, the vaccine also showed impact against severe diarrhea of any cause. "This is an important scientific breakthrough against rotavirus infections, the most severe and lethal cause of childhood diarrhea, responsible for approximately 100,000 deaths of small children in India each year," said DBT Secretary Dr K. Vijay Raghavan. "The clinical results indicate that the vaccine, if licensed, could save the lives of thousands of children each year in India." The vaccine was developed through a unique social innovation partnership that brought together the experience and expertise of Indian and international researchers as well as the public and private sectors. The vaccine originated from an attenuated strain of rotavirus that was isolated from an Indian child at the All India Institute of Medical Sciences in New Delhi in 1985-86. Since then, partners have included DBT, Bharat Biotech, the US National Institutes of Health (NIH), the US Centers for Disease Control and Prevention (CDC), Stanford University School of Medicine, and the nongovernmental organization, PATH.

Mouse Study Suggests Blood Protein May Contribute to Atherosclerosis

On May 10, 2013, the Journal of the American Heart Association published, online, the conclusive results from a study directed by Dr. Éric Thorin of the Montreal Heart Institute (MHI), which suggests for the first time that a blood protein contributes to the early development of atherosclerosis. Dr. Thorin, his team, and his collaborators discovered that the blood levels of angiopoietin-like protein 2 (angptl2) are six times higher in subjects with coronary heart disease than in healthy subjects of the same age. Their basic research study also revealed that angptl2, which is undetectable in young mice, increases with age in healthy subjects and increases prematurely in subjects who have high cholesterol and pre-atherosclerotic lesions. This study was conducted using an animal model consisting of three- to twelve-month-old mice. These results represent a major advance in the prevention and treatment of atherosclerosis. "Although much work remains to be done to broaden our knowledge of this protein's mechanisms of action, angiopoietin-like protein 2 may represent an early biomarker not only to prevent vascular damage, but also to predict atherosclerotic disease," explained Dr. Thorin. For 15 years, Dr. Thorin, a researcher at the MHI Research Centre and full professor at Université de Montréal, has been interested in the evolution of artery function during the aging process and in the underlying mechanisms of atherosclerosis. More specifically, over the past five years, he has looked at the role of this particular protein. Thanks to his work, we now know that angptl2 causes a high degree of vascular inflammation.

“Coffee Ring Effect” Counteracted by Bacterial Surfactants

Ever notice how a dried coffee stain has a thicker outer rim, while the middle of the stain remains almost unsoiled? This “coffee ring effect” also occurs in other materials. Researchers from the Departments of Chemical Engineering and Chemistry at KU Leuven in Belgium have now discovered how to counteract coffee rings with “surfactants,” i.e., soap. The key to the discovery was not a kitchen towel, but a bacterium that counteracts the coffee ring effect at the microscopic level. The findings were published on April 23, 2013 in an open-access article in Nature Communications. When a coffee ring dries, its edges become noticeably darker and thicker. This occurs because the coffee particles move toward the edge of the stain while the water in the liquid evaporates. At a microscopic level, this coffee ring effect can also be seen in liquids with particles of other materials such as plastic and wood. In various industrial applications – applying an even coat of paint or varnish, for example – the coffee ring effect can be particularly troublesome and scientists have long been seeking ways to counteract it. Dr. Raf De Dier and Dr. Wouter Sempels (Departments of Chemical Engineering and Chemistry) have now described a solution based on examples found in nature. Drs. De Dier and Sempels carried out experiments and calculations on nanomaterials, as well as on a particularly promising bacterium, Pseudomonas aeruginosa. Pseudomonas aeruginosa is a dangerous bacterium that can cause infections in open wounds. “A Pseudomonas aeruginosa bacteria colony wants to find as large a breeding ground as possible.

May 12th

Sequencing Shows Spontaneous Mutations Are Major Cause of Congenital Heart Disease

Every year, thousands of babies are born with severely malformed hearts, disorders known collectively as congenital heart disease. Many of these defects can be repaired though surgery, but researchers don't understand what causes them or how to prevent them. New research shows that about 10 percent of these defects are caused by genetic mutations that are absent in the parents of affected children. Although genetic factors contribute to congenital heart disease, many children born with heart defects have healthy parents and siblings, suggesting that new mutations that arise spontaneously—known as de novo mutations—might contribute to the disease. "Until recently, we simply didn't have the technology to test for this possibility," says Howard Hughes Medical Institute (HHMI) investigator Dr. Richard Lifton. Dr. Lifton, who is at the Yale School of Medicine, together with Christine Seidman, an HHMI investigator at Brigham and Women's Hospital and colleagues at Columbia, Mt. Sinai, and the University of Pennsylvania, collaborated to study congenital heart disease through the National Heart, Lung, and Blood Institute's (NHLBI’s) Pediatric Cardiac Genomics Consortium. Using robust sequencing technologies developed in recent years, the researchers compared the protein-coding regions of the genomes of children with and without congenital heart disease and their parents, and found that new mutations could explain about 10 percent of severe cases. The results demonstrated that mutations in several hundred different genes contribute to this trait in different patients, but were concentrated in a pathway that regulates key developmental genes. These genes affect the epigenome, a system of chemical tags that modifies gene expression.

Renaissance in New Drugs for Rare Diseases Reported

Once famously described as "orphan diseases, too small to be noticed, too small to be funded" in the Hollywood film “Lorenzo's Oil,” rare diseases are getting unprecedented attention today among drug manufacturers, who are ramping up research efforts and marketing new medicines that promise fuller lives for children and other patients with these heartbreaking conditions. That's the conclusion of a major examination, published as the cover story of the May 13, 2013 issue of Chemical & Engineering News (C&EN), the weekly newsmagazine of the world's largest scientific society (the American Chemical Society--ACS), of the status of new drugs for the 7,000 conditions that affect 200,000 or fewer patients and fall into the "rare disease" category. The article was written by senior editor Lisa Jarvis after months of interviews with patients, parents, pharmaceutical industry officials, and others. C&EN reaches more than 138,000 scientists, policy-makers, educators, and others around the world. "For most of the last century, people afflicted by rare diseases — especially the parents and families of young children — shared the heartbreak of knowing that medicines to treat their loved ones were little more than a dream," says A. Maureen Rouhi, Ph.D., editor-in-chief of C&EN. "As our story documents in such compelling fashion, that situation is dramatically changing. Pharmaceutical companies are making unprecedented investments in medicines for these enigmatic conditions, popularized in films, and treatments for some are on the way." Jarvis describes how a combination of factors has coalesced to foster a renaissance in drug development for rare diseases.

May 10th

Personalized Medicine Conference Will Focus on Next-Gen Sequencing for Targeted Therapeutics

The sixth annual Personalized Medicine Conference (6.0) organized by San Francisco State University will focus on the amazing technological challenges and advances of “next-generation sequencing,” examining the very latest approaches and how they are leading to profound changes in our understanding of basic biological questions and to more efficacious and cost-effective therapies. The conference is entitled, “Next-Generation Sequencing for Targeted Therapeutics.” Featured speakers include Kimberly J. Popovits, Chairman of the Board, Chief Executive Officer & President of Genomic Health; Dr. Mark Sliwkowski, Distinguished Staff Scientist at Genentech; Professor Atul Butte of Stanford University; and Dr. Carl Borrebaeck, Professor & Chair of Immunotechnology and Director of CREATE Health at Lund University in Sweden. The conference will take place at the South San Francisco Conference Center (http://www.ssfconf.com/directions-top) from 8:00 am to 5:30 pm on Thursday, May 30, 2013, with a reception to follow. Those wishing to attend are urged to register as soon as possible (http://personalizedmedicine.sfsu.edu/register.html). For additional information, to help sponsor the event, or to inquire about special academic rates, contact dnamed@sfsu.edu. The conference organizers, including Michael Goldman, Ph.D., Professor and Chair of San Francisco State’s Department of Biology, noted that with the price of sequencing a complete human genome falling into the $1,000 range, stunning advances are sure to come over the next few years. It is likely that a detailed genome sequence will soon be part of a routine medical history, allowing unprecedented precision in diagnosis and treatment. The DNA and RNA signatures of both complex, common diseases and rare, elusive conditions will yield their secrets.

Cocaine Vaccine Moves Toward Human Clinical Trials

Researchers at the Weill Cornell Medical College in New York City have successfully tested their novel anti-cocaine vaccine in primates, bringing them closer to launching human clinical trials. Their study, published online on May 10, 2013 by the journal Neuropsychopharmacology, used a radiological technique to demonstrate that the anti-cocaine vaccine prevented the drug from reaching the brain and producing a dopamine-induced high. "The vaccine eats up the cocaine in the blood like a little Pac-man before it can reach the brain," says the study's lead investigator, Dr. Ronald G. Crystal, chairman of the Department of Genetic Medicine at Weill Cornell Medical College. "We believe this strategy is a win-win for those individuals, among the estimated 1.4 million cocaine users in the United States, who are committed to breaking their addiction to the drug," he says. "Even if a person who receives the anti-cocaine vaccine falls off the wagon, cocaine will have no effect." Dr. Crystal says he expects to begin human testing of the anti-cocaine vaccine within a year. Cocaine (image), a tiny molecule drug, works to produce feelings of pleasure because it blocks the recycling of dopamine -- the so-called "pleasure" neurotransmitter -- in two areas of the brain, the putamen in the forebrain and the caudate nucleus in the brain's center. When dopamine accumulates at the nerve endings, "you get this massive flooding of dopamine and that is the feel-good part of the cocaine high," says Dr. Crystal. The novel vaccine Dr. Crystal and his colleagues developed combines bits of the common cold virus with a particle that mimics the structure of cocaine. When the vaccine is injected into an animal, its body "sees" the cold virus and mounts an immune response against both the virus and the cocaine mimic, says Dr. Crystal.

Disease-in-a-Dish Models ID Drugs for Possible Treatment of Ataxia Telangiectasia

Led by Dr. Peiyee Lee and Dr. Richard Gatti, researchers at the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA have used induced pluripotent stem (iPS) cells to advance disease-in-a-dish modeling of a rare genetic disorder, ataxia telangiectasia (A-T). Their discovery shows the positive effects of drugs that may lead to effective new treatments for the fatal neurodegenerative disease. iPS cells are made from patients' skin cells, rather than from embryos, and they can become any type of cells, including brain cells, in the laboratory. The study was published online on May 7, 2013 in Nature Communications. People with A-T begin life with neurological deficits that become devastating through progressive loss of function in a part of the brain called the cerebellum, which leads to severe difficulty with movement and coordination. A-T patients also suffer frequent infections due to their weakened immune systems and have an increased risk for cancer. The disease is caused by lost function in a gene, ATM, that normally repairs damaged DNA in the cells and preserves normal function. Developing a human neural cell model to understand A-T's neurodegenerative process — and create a platform for testing new treatments — was critical because the disease presents differently in humans and laboratory animals. Scientists commonly use mouse models to study A-T, but mice with the disease do not experience the more debilitating effects that humans do. In mice with A-T, the cerebellum appears normal and they do not exhibit the obvious degeneration seen in the human brain. Dr. Lee and colleagues used iPS cell–derived neural cells developed from skin cells of A-T patients with a specific type of genetic mutation to create a disease-in-a-dish model.

Genome Sequence of Sacred Lotus Plant Reveals Secrets

The sacred lotus (Nelumbo nucifera) is a symbol of spiritual purity and longevity. Its seeds can survive up to 1,300 years, its petals and leaves repel grime and water, and its flowers generate heat to attract pollinators. Now, researchers report online on May 10, 2013 in an open-access article in Genome Biology that they have sequenced the lotus genome, and the results offer insight into the heart of some of its mysteries. The sequence reveals that of all the plants sequenced so far – and there are dozens – the sacred lotus bears the closest resemblance to the ancestor of all eudicots, a broad category of flowering plants that includes apple, cabbage, cactus, coffee, cotton, grape, melon, peanut, poplar, soybean, sunflower, tobacco, and tomato. The plant lineage that includes the sacred lotus forms a separate branch of the eudicot family tree, and so lacks a signature triplication of the genome seen in most other members of this family, said University of Illinois plant biology and Institute for Genomic Biology professor Ray Ming, who led the analysis with Dr. Jane Shen-Miller, a plant and biology professor at the University of California at Los Angeles (who germinated a 1,300-year-old sacred lotus seed); and Shaohua Li, director of the Wuhan Botanical Garden at the Chinese Academy of Sciences. "Whole-genome duplications – the doubling, tripling (or more) of an organism's entire genetic endowment – are important events in plant evolution," Dr. Ming said. Some of the duplicated genes retain their original structure and function, and so produce more of a given gene product – a protein, for example, he said. Some gradually adapt new forms to take on new functions. If those changes are beneficial, the genes persist; if they're harmful, they disappear from the genome.

May 9th

Confirmation That Justinianic Plague Was Caused by Yersinia pestis

From the several pandemics generally called 'pestilences,' three are historically recognized as due to plague, but only for the third pandemic of the 19th-21st centuries AD were there microbiological evidences that the causing agent was the bacterium Yersinia pestis. "For a long time scholars from different disciplines have intensively discussed about the actual etiological agents of the past pandemics. Only ancient DNA analyses carried out on skeletal remains of plague victims could finally conclude the debate," said Dr. Barbara Bramanti of the Palaeogenetics Group at the Institute of Anthropology at Johannes Gutenberg University Mainz (JGU) in Germany. About two years ago, she headed the international team which demonstrated beyond any doubt that Y. pestis also caused the second pandemic of the 14th-17th centuries including the Black Death, the infamous epidemic that ravaged Europe from 1346-1351. Dr. Bramanti and her Mainz colleague Dr. Stephanie Hänsch have now cooperated with the University of Munich, the German Bundeswehr, and international scholars to solve the debate as to whether Y. pestis also caused the so-called Justinianic Plague of the 6th-8th centuries AD. The results of ancient DNA analyses carried out remains in the early medieval cemetery of Aschheim in Bavaria were published online on May 2, 2103 in PLOS Pathogens. These results confirmed unambiguously that Y. pestis was indeed the causing agent of the first pandemic, in contrast to what has been postulated by other scientists recently. This revolutionary result is supported by the analysis of the genotype of the ancient strain which provides information about the phylogeny and the place of origin of this plague.