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Archive - Apr 2011

April 20th

New Insight into Survival Strategy of Sleeping Sickness Parasite

Fresh insight into the survival strategy of the parasite that causes sleeping sickness could help inform new treatments for the disease. Scientists have found that the parasite, which can transform itself into either of two physical forms, has developed a careful balance between these. One of these types ensures infection in the bloodstream of a victim, and the other type is taken up by the tsetse fly and spread to another person or animal. The parasite maintains a trade-off between maintaining enough parasites to beat off the immune response and cause infection, and ensuring sufficient parasites to enable the spread of the disease. Researchers at the University of Edinburgh, who carried out the study, used a combination of biological and mathematical techniques to show how the parasite balances production of each of the forms as it causes an infection. Their results enable fresh understanding of how the parasite reacts to its surroundings to ensure its survival in the short term as well as the long-term spread of the disease. Sleeping sickness, which is spread by the bite of the tsetse fly, affects some 30,000 people in sub-Saharan Africa. Many millions more are considered to be at risk. The disease affects people and animals and without treatment is considered fatal. The research, funded by the Wellcome Trust, was published in the April 21, 2011 issue of the journal Cell Host & Microbe. Professor Keith Matthews of the University of Edinburgh, who led the study, said: "Sleeping sickness parasites alter their form in order to ensure their survival and spread.

Close Relative of Arabidopsis Has Much Bigger Genome

It would appear reasonable to assume that two closely related plant species would have similar genetic blueprints. However, scientists from the Max Planck Institute for Developmental Biology in Tübingen, working in cooperation with an international research team have now decoded, for the first time, the entire genome of the lyre-leaved rock cress (Arabidopsis lyrata), a close relative of the thale cress (Arabidopsis thaliana), a model plant used by geneticists. They discovered that the genome of the lyre-leaved rock cress is fifty percent bigger than that of the thale cress. Moreover, these changes arose over a very short period in evolutionary terms. This new high-quality genome analysis will provide a basis for further detailed comparative studies on the function, ecology and evolution of the plant genus Arabidopsis. Genome size among the different species of the plant kingdom varies significantly. At the upper end of the currently known spectrum, scientists have identified the herb Paris or true-lover’s knot (Paris quadrifolia), whose genome is a good thousand times longer than that of the carnivorous plants from the genus Genlisea. However, these plants are so distantly related that it is almost impossible to identify the evolutionary forces at work in the individual species. Therefore, researchers from Dr. Detlef Weigel’s Department of Molecular Biology at the Max Planck Institute for Developmental Biology in Tübingen working in cooperation with an international research team selected for their genome study a species closely related to the thale cress (Arabidopsis thaliana), probably the most widely studied flowering plant in genetics. The species in question was lyre-leaved rock cress (Arabidopsis lyrata) which, unlike thale cress, is unable to self-fertilize.

Placenta Synthesizes Serotonin for Developing Fetus

Research at the Keck School of Medicine of the University of Southern California's (USC) Zilkha Neurogenetic Institute shows for the first time that the human placenta plays an active role in synthesizing serotonin, paving the way to new treatment strategies that could mitigate health impacts such as cardiovascular disease and mental illness. The groundbreaking findings, conducted with researchers from Vanderbilt University as part of a Silvio Conte Center of Excellence grant from the National Institute of Mental Health, offer conclusive evidence that the placenta provides serotonin to the fetal forebrain, not through the mother's blood supply, as theorized for the past 60 years. The research was published in Nature on April 21, 2011. "Our research indicates that the placenta actually synthesizes serotonin, and the serotonin is released from the placenta into the fetal bloodstream where it can reach the fetal brain," said lead author Dr. Alexandre Bonnin. "The placenta was seen as a passive organ, but we now know that it has significant synthetic capabilities and has a much more critical role in developmental programming of the fetus than previously thought.” Dr. Bonnin's work with Dr. Pat Levitt, director of the Zilkha Neurogenetic Institute and corresponding author on the paper, included the invention of a unique technology known as a "placentometer" that monitors substances that pass through the mouse placenta from mother to fetus. This technology can incorporate genetic models of human disease, and could lead to targeted therapies that treat the mother without affecting the fetus, or vice versa. "The findings by Dr.

April 20th

Nutlin-3a Activates p53, Stimulates Apoptosis in Glioblastoma Cells

Researchers of Apoptosis and Cancer Group of the Bellvitge Biomedical Research Institute (IDIBELL) have found that a small molecule, Nutlin-3a, an antagonist of MDM2 protein, stimulates the signaling pathway of another protein, p53. In this way, it induces cell death and senescence (loss of proliferative capacity) in brain cancer, a fact that slows the cancer’s growth. These results open the door for MDM2 agonists as new treatments for glioblastomas. The study was published online on April 5, 2011, in the journal PLOS One. Glioblastoma multiforme is the most common brain tumor in adults and the most aggressive. Despite efforts on new treatments and technological innovation in neurosurgery, radiation therapy, and clinical trials of new therapeutic agents, most patients die two years after diagnosis. Dr. Avelina Tortosa, IDIBELL and University of Barcelona (UB) researcher, coordinator of the study, explained that one objective of her group is "to find substances that sensitize tumor cells to radiotherapy for more efficient treatments.” There is evidence that several genetic alterations promote the growth, invasion, and resistance to stimuli that induce programmed cell death (apoptosis). Along these lines, the pilot project TCGA (The Cancer Genome Atlas) has sequenced the genome of up to 25 glioblastomas noting that 14% of patients have an increased expression of MDM2 and 35% had alterations in p53 expression (apoptosis-inducing). That's why research is now focused on the development of new therapeutic strategies that target the apoptosis in gliomas. The aim of this study was to investigate the antitumor activity of Nutlin-3a in cell lines and primary cultures of glioblastoma.

April 18th

Compound Halts Progression of Multiple Sclerosis in Animal Models

Scientists from the Florida campus of The Scripps Research Institute have developed the first of a new class of highly selective compounds that effectively suppresses the severity of multiple sclerosis in animal models. The new compound could provide new and potentially more effective therapeutic approaches to multiple sclerosis and other autoimmune diseases that affect patients worldwide. The study appeared April 17, 2011, in an advance online edition of Nature. Current treatments for autoimmunity suppress the patient's entire immune system, leaving patients vulnerable to a range of adverse side effects. Because the new compound, known as SR1001, only blocks the actions of a specific cell type playing a significant role in autoimmunity, it appears to avoid many of the widespread side effects of current therapies. "This is a novel drug that works effectively in animal models with few side effects," said Dr. Tom Burris, a professor in the Department of Molecular Therapeutics at Scripps Florida who led the study, which was a multidisciplinary collaboration with scientists including Drs. Patrick Griffin, William Roush, and Ted Kamenecka of Scripps Research, and Dr. Paul Drew of the University of Arkansas for Medical Sciences. "We have been involved in several discussions with both pharmaceutical and biotechnology firms who are very interested in developing it further." A lengthy process of drug development and review is required to ensure a new drug's safety and efficacy before it can be brought to market. "This impressive multidisciplinary team has used a combined structural and functional approach to describe a class of molecules that could lead to new medicines for treating autoimmune diseases," said Dr. Charles Edmonds, who oversees structural biology grants at the National Institutes of Health.

April 17th

FGF9 Appears to Aid Regeneration of Blood Supply in Damaged Tissue

Researchers at The University of Western Ontario have discovered a strategy for stimulating the formation of highly functional new blood vessels in tissues that are starved of oxygen. Dr. Geoffrey Pickering and Matthew Frontini at the Schulich School of Medicine & Dentistry developed a strategy in which a biological factor, called fibroblast growth factor 9 (FGF9), is delivered at the same time that the body is making its own effort at forming new blood vessels in vulnerable or damaged tissue. The result is that an otherwise unsuccessful attempt at regenerating a blood supply becomes a successful one. Their findings were published online in Nature Biotechnology on April 17, 2011. "Heart attacks and strokes are leading causes of death and disability among Canadians. Coronary bypass surgery and stenting are important treatments but are not suitable for many individuals," explains Dr. Pickering, a professor of Medicine (Cardiology), Biochemistry, and Medical Biophysics, and a scientist at the Robarts Research Institute. "Because of this, there has been considerable interest in recent years in developing biological strategies that promote the regeneration of a patient's own blood vessels." This potential treatment has been termed 'therapeutic angiogenesis'. "Unfortunately and despite considerable investigation, therapeutic angiogenesis has not as yet been found to be beneficial to patients with coronary artery disease. It appears that new blood vessels that form using approaches to date do not last long, and may not have the ability to control the flow of blood into the areas starved of oxygen." The work of Dr. Pickering and collaborators provides a method to overcome these limitations.

New Therapeutic Target for Asthma, COPD and Other Lung Disorders

Dr. Michael Croft, a researcher at the La Jolla Institute for Allergy & Immunology, and colleagues have discovered a molecule's previously unknown role as a major trigger for airway remodeling, which impairs lung function, making the molecule a promising therapeutic target for chronic asthma, chronic obstructive pulmonary disease (COPD) and several other lung conditions. A scientific paper on Dr. Croft's finding was published online on April 17, 2011, in Nature Medicine. The finding marks Dr. Croft's second major discovery with therapeutic potential for asthma. His previous finding, of a novel molecular mechanism driving lung inflammation, is the basis for a potential asthma treatment now in Phase II human clinical trials. "Dr. Croft's continued efforts to uncover the cellular pathways influencing asthma and other lung disorders have produced remarkable results," said Dr. Mitchell Kronenberg, La Jolla Institute president and chief scientific officer. "He is a researcher of the highest caliber and I believe his discoveries will someday improve the lives of millions of people around the world." In the Nature Medicine paper entitled, "The tumor necrosis factor family member LIGHT is a target for asthmatic airway remodeling," Dr. Croft and colleagues showed that blocking LIGHT's interactions with its two receptors significantly inhibited the process of airway remodeling in mouse models of chronic asthma. Airway remodeling refers to inflammation-fueled structural changes in the lungs, including fibrosis, which can occur over time and result in declining lung function that strongly contributes to conditions such as COPD, chronic asthma, and several other respiratory disorders. Asthma affects more than 20 million Americans, including nine million children, and is the third-ranking cause of hospitalization among U.S.

FDA Approves Treatment Device for Recurrent Glioblastoma

On April 14, 2011, Novocure announced that the U.S. Food and Drug Administration (FDA) approved the NovoTTF-100A System (NovoTTF) for the treatment of adult patients with glioblastoma multiforme (GBM) brain tumors, following tumor recurrence after receiving chemotherapy. The portable, wearable device delivers an anti-mitotic, anti-cancer therapy as patients maintain their normal daily activities. The NovoTTF is a novel, first-in-class treatment option for patients and physicians battling glioblastoma. "Our device provides patients and physicians with a novel, non-invasive alternative to chemotherapy that is safe and effective," said Dr. Eilon Kirson, Novocure's Chief Medical Officer. "The device allows for continuous treatment without the usual, debilitating side effects that chemotherapies inflict on recurrent GBM patients and indirectly on their families." The NovoTTF-100A System is a portable, non-invasive medical device designed for continuous use throughout the day by the patient. The device has been shown in in vitro studies to slow and reverse tumor growth by inhibiting mitosis, the process by which cells divide and replicate. The NovoTTF-100A device, which weighs about six pounds (three kilograms), creates a low intensity, alternating electric field within the tumor that exerts physical forces on electrically charged cellular components, preventing the normal mitotic process and causing cancer cell death prior to division. Novocure currently has US and European marketing approvals for the NovoTTF-100A. Results from a 237 patient randomized pivotal trial demonstrated that compared to patients treated with chemotherapy, NovoTTF-treated patients achieved comparable median overall survival times, had fewer side effects, and reported improved quality of life scores.

April 15th

Analysis Indicates Human Speech Arose in Africa

An analysis of language from around the world suggests that human speech originated – just once – in central and southern Africa. Verbal communication then likely spread around the globe, evolving alongside migrating human populations, according to Dr. Quentin Atkinson, reporting in the April 15 issue of Science. The researcher from New Zealand studied the phonemes, or the perceptually distinct units of sound that differentiate words, used in 504 human languages today and found that the dialects containing the most phonemes are spoken in Africa while those with the fewest phonemes are spoken in South America and on tropical islands in the Pacific Ocean. The author notes that this pattern of phoneme usage around the world mirrors the pattern of human genetic diversity, which also declined as humans expanded their range from Africa to colonize other regions. In general, the areas of the globe that were most recently colonized incorporate fewer phonemes into the local languages whereas the areas that have hosted human life for millennia (particularly sub-Saharan Africa) still use the most phonemes. This decline in phoneme usage cannot be explained by demographic shifts or other local factors, and it provides strong evidence for an African origin of modern human languages – as well as parallel mechanisms that slowly shaped both genetic and linguistic diversity among humans. [Science abstract]

Potential New Target for Treatment of Neurofibromatosis Type 2

The proteins that provide cells with a sense of personal space could lead to a therapeutic target for neurofibromatosis type 2 (NF2), an inherited cancer disorder, according to researchers at The Wistar Institute and collaborating institutions. The findings, which appear in the April 12 issue of the journal Cancer Cell, could have profound implications for NF2 and related cancers, such as mesothelioma. The researchers describe, for the first time, that Merlin, the protein encoded by the NF2 gene interacts with a protein called angiomotin. This connection between Merlin and angiomotin also brings together two important information networks in cells, both of which have been implicated in numerous forms of cancer. It is a connection, the researchers say, between the sensors that detect interactions between cells and the signaling networks that drive cell division. "Angiomotin is required for movement of cells that form new blood vessels, so it is fascinating to see it so closely linked to Merlin, the product of the NF2 gene, loss of which leads to tumor formation," said Dr. Joseph Kissil, senior author of the study and associate professor in the Molecular and Cellular Oncogenesis Program of The Wistar Institute Cancer Center. "The discovery opens up a potential new method to treat NF2 by attacking the tumor cells directly and by starvation, a strategy already employed in certain cancer therapies. Drugs like Avastin, for example, target the growing blood vessels," Kissil said, "but what makes angiomotin a tempting target is that it is used by both blood vessels and the growing tumor cells that need the nutrients these blood vessels provide." NF2 is a genetic disorder caused by a mutation in both copies of a person's NF2 gene. It occurs in about one in every 30,000 people, and it is mostly hereditary.