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Archive - Nov 2012

Date

November 11th

Schizophrenia Genetic Networks Identified; Connection to Autism Found

Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify. In the past few years, researchers have implicated several genes, but it is unclear how they act to produce the disorder. A new study by researchers at Columbia University Medical Center identifies affected gene networks and provides insight into the molecular causes of the disease. The paper was published November 11, 2012 in the online edition of the journal Nature Neuroscience. Using an unbiased collection of hundreds of mutations associated with schizophrenia, the Columbia researchers applied a sophisticated computational approach to uncover hidden relationships among seemingly unrelated genes. The analysis revealed that many of the genes mutated in schizophrenia are organized into two main networks, which take part in a few key processes, including axon guidance, synapse function, neuron mobility, and chromosomal modification. The study also uncovered an intriguing connection between schizophrenia and autism. "If we hadn't known that these were two different diseases, and had put all the mutations into a single analysis, it would have come up with very similar networks," said the study's senior author, Dennis Vitkup, Ph.D., associate professor in the Department of Biomedical Informatics, the Center for Computational Biology and Bioinformatics, and the Columbia Initiative in Systems Biology at Columbia University Medical Center. "It shows how closely the autism and schizophrenia genetic networks are intertwined," he added. Although it will take time to translate the findings into practical treatments, the study provides insight into the molecular causes of schizophrenia.

Mutations in Genes That Modify DNA Packaging Result in Facioscapulohumeral Muscular Dystrophy (FSHD)

A recent finding by medical geneticists sheds new light on how facioscapulohumeral muscular dystrophy develops and how it might be treated. More commonly known as FSHD, the devastating disease affects both men and women. FSHD is usually an inherited genetic disorder, yet sometimes appears spontaneously via new mutations in individuals with no family history of the condition. "People with the condition experience progressive muscle weakness and about 1 in 5 require wheelchair assistance by age 40," said Dr. Daniel G. Miller, University of Washington (UW) associate professor of pediatrics in the Division of Genetic Medicine. Dr. Miller and his worldwide collaborators study the molecular events leading to symptoms of FSHD in the hopes of designing therapies to prevent the emergence of symptoms or reduce their severity. In the November 11, 2012 online issue of Nature Genetics, Dr. Miller and Dr. Silvere M. van der Maarel of Leiden University in The Netherlands, along with an international team, report their latest findings on the role of epigenetic modifications in causing the disease. In Seattle, Dr. Stephen Tapscott of the Fred Hutchinson Cancer Research Center was also a major contributor to the project. He is a UW professor of neurology and a researcher at the UW Center for Human Development and Disability. Epigenetics refers to mechanisms that influence how the genome is regulated and how, where, and when genes act -- all without altering the underlying DNA sequence. The flexibility of DNA packaging – its wrapping, which can be tightened and loosened, and its chemical tags – is one of the epigenetic forces on the genome. This packaging is called the chromatin structure and is one way specialized cells such as those in our muscles allow groups of genes to be shut off, or be available for expression.

Age-Related Wet Macular Degeneration Treatment Effective Even with Macular Traction Problems

The primary treatment for wet macular degeneration, a chronic eye condition that causes vision loss, is effective even if patients have macular traction problems, a Mayo Clinic study shows. The findings were presented November 11, 2012 at the annual meeting of the American Academy of Ophthalmology in Chicago. Due to the aging population, an increasing number of patients are being treated for age-related macular degeneration (AMD), an eye condition in which abnormal blood vessels develop and leak into the eye. When patients develop wet AMD, they receive injections of anti-vascular endothelial growth factor medication (VEGF). VEGF prompts growth of new blood vessels in the body. In the case of AMD, however, such new growth is unwanted and may cause bleeding in the retina. It has not been clear whether this treatment would also serve patients experiencing other symptoms, such as vitreomacular interface disease (VMID), in which there is traction or contact between the retina and the vitreous matter in the eye. Mayo researchers retrospectively studied 178 patients, of whom 18 percent had VMID over an average of 2.5 years. Findings showed that while eyes with some kind of macular traction required more injections, they still showed improvement (best corrected visual acuity) to similar eyes without VMID. "This finding is significant," says senior author Sophie J. Bakri, M.D., "because it showed that patients with VMID are not necessarily treatment resistant for AMD." She also says it may help physicians not give up on treating such patients, and understand the need for more doses of medication for those with VMID. Researchers say more study is needed, including a prospective clinical trial. Co-authors include Amy Green-Simms, M.D., and Blake Fechtel and Zubin Agarwal, M.P.H., all of the Mayo Clinic.

Texas Cotton Getting a Genetic “Tune-Up”

Can you imagine trying to build a competitive race car with old parts? Chances are, the entry would not fare well at the Indy 500. Very much the same thing might be said about today's crops, according to a Texas A&M AgriLife Research scientist. "Contemporary crops such as Texas cotton are like finely tuned racing machines — they need high quality parts to perform optimally," said Dr. David Stelly, AgriLife Research cotton geneticist in College Station. "And they constantly need new ones to replace ones that are no longer functional, as well as those that are still effective, but no longer at the cutting edge of competition." Dr. Stelly said his role in the AgriLife Research cotton breeding program is to infuse new genes and gene combinations into the genetics and breeding research arena, "so that we can utilize natural genetic resources to help meet the many challenges breeding programs face." Transferring genes into a cultivated crop from a wild species “is like swimming upstream, one is fighting all sorts of biological and genetic barriers," he said. For years, he and his long-time research assistant, Dwaine Raska, have been transferring the alien genes by a special breeding process called "chromosome substitution." "Using chromosome substitution, we can target one pair of cultivated cotton chromosomes at a time, and replace it with the corresponding pair of chromosomes from a wild species chosen as the donor. On average, each substitution replaces about 2,000 cotton genes with donor genes," Dr. Stelly said. Having already developed chromosome substitution lines for many chromosomes from three donor species, Dr. Stelly is working in collaboration with a former graduate student, Dr. Sukumar Saha, now with the U.S.

Scent Markings May Be Used to Stop Endangered African Wild Dogs from Wandering into Extinction

Throughout history, and all over the world, people have killed wild carnivores to protect their livestock. Now, a relentless expansion of human activities that brings people and their livestock into ever larger areas of former wildlife habitat is rapidly escalating both the threats to carnivore populations and the impact of carnivores on rural people’s liveliehoods. In southern Africa a radically new way to reduce conflict between people and wild carnivores is being developed by the BioBoundary Project of the Botswana Predator Conservation Trust (BPCT, http://www.bpctrust.org/). With funding from the Paul G. Allen Family Foundation, the BioBoundary Project is using the protection of endangered African wild dogs as a test case of whether wild carnivores can be kept away from livestock by artifical scent-mark boundaries between protected wildlife areas and livestock areas. African wild dogs (Lycaon pictus) are intensely social super-predators. They live in packs with huge home ranges that extend beyond the boundaries of even the largest of protected areas. When wild dogs cross these boundaries into landscapes that are dominated by humans and livestock they run a gauntlet of shooting, snaring, and poisoning; in most wild dog populations, more dogs are killed by people than by anything else. African wild dogs used to range across 39 sub-Saharan countries but now their numbers have dwindled to fewer than 6,000 and only two populations are large enough to be self-sustaining in the long term. Each African wild dog pack stakes out its territory by soaking patches of soil with the urine of the pack’s alpha pair.

November 10th

Ancient Genetic Building Block Discovered in Cyanobacteria

Scientists believe that prior to the advent of DNA as the earth’s primary genetic material, early forms of life used RNA to encode genetic instructions. What sort of genetic molecules did life rely on before RNA? The answer may be AEG, a small molecule that when linked into chains forms a hypothetical backbone for peptide nucleic acids (PNA), which have been hypothesized as the first genetic molecules. Synthetic AEG has been studied by the pharmaceutical industry as a possible gene silencer to stop or slow certain genetic diseases. The only problem with the theory is that up to now, AEG has been unknown in nature. A team of scientists from the USA and Sweden announced that they have discovered AEG within cyanobacteria which are believed to be some of the most primitive organisms on earth. Cyanobacteria sometimes appear as mats or scums on the surface of reservoirs and lakes during hot summer months. Their tolerance for extreme habitats is remarkable, ranging from the hot springs of Yellowstone to the tundra of the Arctic. “Our discovery of AEG in cyanobacteria was unexpected,” explains Dr. Paul Alan Cox, co-author of the paper that appeared November 7, 2012 in the journal PLoS ONE. The American team is based at the Institute for Ethnomedicine in Jackson Hole, Wyoming, and serves as adjunct faculty at Weber State University in Ogden, Utah. “While we were writing our manuscript,” Dr. Cox says, “we learned that our colleagues at the Stockholm University Department of Analytical Chemistry had made a similar discovery, so we asked them to join us on the paper.” To determine how widespread AEG production is among cyanobacteria, the scientists analyzed pristine cyanobacterial cultures from the Pasteur Culture Collection of Paris, France.

Resveratrol Could Be Key to Fighting Prostate Cancer

Resveratrol, a compound found commonly in grape skins and red wine, has been shown to have several beneficial effects on human health, including cardiovascular health and stroke prevention. Now, a University of Missouri (MU) researcher has discovered that the compound can make prostate tumor cells more susceptible to radiation treatment, increasing the chances of a full recovery from all types of prostate cancer, including aggressive tumors. "Other studies have noted that resveratrol made tumor cells more susceptible to chemotherapy, and we wanted to see if it had the same effect for radiation therapy," said Dr. Michael Nicholl, an assistant professor of surgical oncology in the MU School of Medicine. "We found that when exposed to the compound, the tumor cells were more susceptible to radiation treatment, but that the effect was greater than just treating with both compounds separately." Prostate tumor cells contain very low levels of two proteins, perforin and granzyme B, which can function together to kill cells. However, both proteins need to be highly "expressed" to kill tumor cells. In his study, when Dr. Nicholl introduced resveratrol into the prostate tumor cells, the activity of the two proteins increased greatly. Following radiation treatment, Nicholl found that up to 97 percent of the tumor cells died, which is a much higher percentage than treatment with radiation alone. "It is critical that both proteins, perforin and granzyme B, are present in order to kill the tumor cells, and we found that the resveratrol helped to increase their activity in prostate tumor cells," Dr. Nicholl said. "Following the resveratrol-radiation treatment, we realized that we were able to kill many more tumor cells when compared with treating the tumor with radiation alone.

November 9th

Micro RNAs in Plants: Regulation of the Regulator

Micro RNAs are essential regulators of the genetic program in multicellular organisms. Because of their potent effects, the production of these small regulators has itself to be tightly controlled. That is the key finding of a new study performed by Tübingen scientists at the Max Planck Institute for Developmental Biology. They identified a new component that modulates the production of micro RNAs in thale cress, Arabidopsis thaliana, by the removal of phosphate residues from a micro RNA-biogenesis enzyme. This can be as quick as the turn of a switch, allowing the plant to adapt to changing conditions. In this study, the scientists combined advanced imaging for facile detection of plants with defective micro RNA activity with whole genome sequencing for rapid identification of new mutations. The cell seems to thwart itself: Reading the DNA, a mobile messenger RNA is produced in the cell nucleus, exported to the cytoplasm where it serves as a blueprint for the production of proteins. At the same time, the cell is able to produce micro RNAs that, by binding to specific messenger RNAs, can block protein production or even initiate its destruction. But why does the cell start a costly process and immediately stops it? "Well, the answer lies on the fine balance the cell has to achieve between producing a protein and avoid(ing) having an excess of it. Reaching the right level of a protein and its adequate temporal and spatial distribution requires, sometimes, opposed forces," says Dr. Pablo Manavella, first author of the study, published in the November 9, 2012 issue of Cell, and a postdoc in the department of Dr. Detlef Weigel at the Max Planck Institute for Developmental Biology. "Once the transcript of the messenger RNA is activated it is quite stable.

RTS,S Candidate Vaccine Reduces Malaria by One-Third in African Infants

Results from a pivotal, large-scale Phase III trial, published online on November 9, 2012 in the New England Journal of Medicine, show that the RTS,S malaria vaccine candidate can help protect African infants against malaria. When compared to immunization with a control vaccine, infants (aged 6-12 weeks at first vaccination) vaccinated with RTS,S had one-third fewer episodes of both clinical and severe malaria and had similar reactions to the injection. In this trial, RTS,S demonstrated an acceptable safety and tolerability profile. Eleven African research centers in seven African countries are conducting this trial, together with GlaxoSmithKline (GSK) and the PATH Malaria Vaccine Initiative (MVI), with grant funding from the Bill & Melinda Gates Foundation to MVI. Dr. Salim Abdulla, a principal investigator for the trial from the Ifakara Health Institute, Tanzania, said: "We've made significant progress in recent years in our battle against malaria, but the disease still kills 655,000 people a year—mainly children under five in sub-Saharan Africa. An effective malaria vaccine would be a welcome addition to our tool kit, and we've been working toward this goal with this RTS,S trial. This study indicates that RTS,S can help to protect young babies against malaria. Importantly, we observed that it provided this protection in addition to the widespread use of bed nets by the trial participants." When administered along with standard childhood vaccines, the efficacy of RTS,S in infants aged 6 to 12 weeks (at first vaccination) against clinical and severe malaria was 31% and 37%, respectively, over 12 months of follow-up after the third vaccine dose. Insecticide-treated bed nets were used by 86% of the trial participants, which demonstrated that RTS,S provided protection beyond existing malaria control interventions.

November 8th

New Cells Could Be Useful in Treating Blinding Eye Conditions

Eye experts and scientists at the University of Southampton have discovered specific cells in the eye that could lead to a new procedure to treat and cure blinding eye conditions. Led by Professor Andrew Lotery, the study found that cells called corneal limbal stromal cells, taken from the front surface of the eye, have stem cell properties and could be cultured to create retinal cells. This could lead to new treatments for eye conditions such as retinitis pigmentosa or wet age-related macular degeneration, a condition which is a common cause of loss of vision in older people and will affect around one in three people in the UK by age 70. Furthermore, the research, published online on September 5, 2012 in the British Journal for Ophthalmology, suggests that using corneal limbus cells would be beneficial in humans as it would avoid complications with rejection or contamination because the cells taken from the eye would be returned to the same patient. Professor Lotery, who is also a Consultant Ophthalmologist at Southampton General Hospital, comments: “This is an important step for our research into the prevention and treatment of eye conditions and blindness. We were able to characterize the corneal limbal stromal cells found on the front surface of the eye and identify the precise layer in the cornea that they came from. We were then successful in culturing them in a dish to take on some of the properties of retinal cells. We are now investigating whether these cells could be taken from the front of the eye and be used to replace diseased cells in the back of the eye in the retina.