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Archive - 2012

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.

Clots Can Sense Blood Flow

The disease atherosclerosis involves the buildup of fatty tissue within arterial walls, creating unstable structures known as plaques. These plaques grow until they burst, rupturing the wall and causing the formation of a blood clot within the artery. These clots also grow until they block blood flow; in the case of the coronary artery, this can cause a heart attack. New research from the University of Pennsylvania has shown that clots forming under arterial-flow conditions have an unexpected ability to sense the surrounding blood moving over them. If the flow stops, the clot senses the decrease in flow and this triggers a contraction similar to that of a muscle. The contraction squeezes out water, making the clot denser. Better understanding of the clotting dynamics that occur in atherosclerosis, as opposed to the dynamics at play in closing a wound, could lead to more effective drugs for heart attack prevention. The research was conducted by graduate student Ryan Muthard and Dr. Scott Diamond, professor and chair of the Department of Chemical and Biomolecular Engineering in the School of Engineering and Applied Science. Their work was published online on October 18, 2012 in the journal Arteriosclerosis, Thrombosis, and Vascular Biology, which is published by the American Heart Association. “Researchers have known for decades that blood sitting in a test tube will clot and then contract to squeeze out water,” Muthard said. “Yet clots observed inside injured mouse blood vessels don’t display much contractile activity. We never knew how to reconcile these two studies, until an unexpected observation in the lab.” Using a specially designed microfluidic device, the researchers pulsed fluorescent dye across a clot to investigate how well it blocked bleeding.

Soldier Beetle Defense Genes May Be Biotech Opportunity

New antibiotic and anti-cancer chemicals may one day be synthesized using biotechnology, following CSIRO's discovery of the three genes that combine to provide soldier beetles with their potent predator defense system. CSIRO researchers, and a colleague at Sweden's Karolinska Institute, published details of the gene identification breakthrough and potential applications online on October 23, 2012 in the international journal Nature Communications. "For the first time, our team has been able to isolate and replicate the three genes that combine to make the potent fatty acid that soldier beetles secrete to ward off predators and infection," said CSIRO Ecosystem Sciences research leader Dr. Victoria Haritos. "This discovery is important because it opens a new way for the unusual fatty acid to be synthesized for potential antibiotic, anti-cancer, or other industrial purposes," Dr Haritos said. Soldier beetles exude a white viscous fluid from their glands to repel potential attacks from predators, as well as in a wax form to protect against infection. The team found this fluid contains an exotic fatty acid called dihydromatricaria acid, or DHMA, which is one of a group called polyynes that have known anti-microbial and anti-cancer properties. While DHMA and similar polyyne fatty acids are found in a wide variety of plants, fungi, liverworts, mosses, marine sponges, and algae, these compounds have proved very difficult to manufacture using conventional chemical processes. However, Dr. Haritos and her team have developed a way to achieve this. "We have outlined a method for reproducing these polyyne chemicals in living organisms like yeast, using mild conditions," Dr Haritos said. Soldier beetles are the only animals reported to contain DHMA.

Highly Sensitive Sense of Touch Found in Crocodiles and Alligators

Crocodiles and alligators are notorious for their thick skin and well-armored bodies. So it comes as something of a surprise to learn that their sense of touch is one of the most acute in the animal kingdom. The crocodilian sense of touch is concentrated in a series of small, pigmented domes that dot their skin all over their body. In alligators, the spots are concentrated around their face and jaws. A new study, published as the cover story of the December 2012 issue of the Journal of Experimental Biology, has revealed that these spots contain a concentrated collection of touch sensors that make them even more sensitive to pressure and vibration than human fingertips. "We didn't expect these spots to be so sensitive because the animals are so heavily armored," said Duncan Leitch, the graduate student who performed the studies under the supervision of Dr. Ken Catania, Stevenson Professor of Biological Sciences at Vanderbilt. Scientists who have studied crocodiles and alligators have taken note of these spots, which they have labeled "integumentary sensor organs" or ISOs. Over the years they have advanced a variety of different hypotheses about their possible function. These include: source of oily secretions that keep the animals clean; detection of electric fields; detection of magnetic fields; detection of water salinity; and, detection of pressure and vibrations. In 2002, a biologist at the University of Maryland reported that alligators in a darkened aquarium turned to face the location of single droplets of water even when their hearing was disrupted by white noise. She concluded that the sensor spots on their faces allowed them to detect the tiny ripples that the droplets produced. "This intriguing finding inspired us to look further," Dr. Catania said.

November 7th

Stem Cells and Nanofibers Yield Promising Nerve Research

Every week in his clinic at the University of Michigan, neurologist Joseph Corey, M.D., Ph.D., treats patients whose nerves are dying or shrinking due to disease or injury. He sees the pain, the loss of ability, and the other effects that nerve-destroying conditions cause – and wishes he could give patients more effective treatments than what's available, or regenerate their nerves. Then he heads to his research lab at the VA Ann Arbor Healthcare System (VAAAHS), where his team is working toward that exact goal. In new research published in several recent papers, Dr. Corey and his colleagues from the U-M Medical School, VAAAHS, and the University of California, San Francisco (UCSF) report success in developing polymer nanofiber technologies for understanding how nerves form, why they don't reconnect after injury, and what can be done to prevent or slow damage. Using polymer nanofibers thinner than human hairs as scaffolds, researchers coaxed a particular type of brain cell to wrap around nanofibers that mimic the shape and size of nerves found in the body. They've even managed to encourage the process of myelination – the formation of a protective coating that guards larger nerve fibers from damage. They began to see multiple concentric layers of the protective substance called myelin start to form, just as they do in the body. Together with the laboratory team of their collaborator Dr. Jonah Chan at UCSF, the authors reported their findings in Nature Methods online on July 15, 2012. The research involves oligodendrocytes, which are the supporting actors to neurons -- the "stars" of the central nervous system. Without oligodendrocytes, central nervous system neurons can't effectively transmit the electrical signals that control everything from muscle movement to brain function.

New Drug Target Found for Cystic Fibrosis

Vancouver researchers have discovered the cellular pathway that causes lung-damaging inflammation in cystic fibrosis (CF), and determined that reducing the pathway’s activity also decreases inflammation. The finding offers a potential new drug target for treating CF lung disease, which is a major cause of illness and death for people with CF. “Developing new drugs that target lung inflammation would be a big step forward,” says Dr. Stuart Turvey, who led the research. Dr. Turvey is the director of clinical research and senior clinician scientist at the Child & Family Research Institute and a pediatric immunologist at BC Children’s Hospital. He is an associate professor in the Department of Pediatrics at the University of British Columbia. The research was published online on October 26, 2012 in the Journal of Immunology. For the study, researchers compared the immune response of normal lung cells with that of CF lung cells after exposing both types of cells to bacteria in the lab. In healthy cells, exposure to bacteria triggers the cell to secrete special molecules that attract immune cells to fight the infection. In CF lung cells, the researchers discovered that a series of molecular events called the unfolded protein response is more highly activated. It causes the CF lung cells to secrete more molecules that attract an excessive amount of immune cells, which leads to increased inflammation. They also found that treating the CF cells with a special chemical normalized the unfolded protein response and stabilized the cells’ immune response. CF is the most common genetic disease affecting young Canadians. One in every 3,600 children born in Canada has CF. There is no cure.

High SFRP4 Protein Reveals Diabetes Risk Many Years in Advance

When a patient is diagnosed with type 2 diabetes, the disease has usually already progressed over several years and damage to areas such as blood vessels and eyes has already taken place. To find a test that indicates who is at risk at an early stage would be valuable, as it would enable preventive treatment to be put in place. Researchers at Lund University in Sweden, together with colleagues, have now identified a promising candidate for a test of this kind. The findings were published in the November 7, 2012 issue of Cell Metabolism. "We have shown that individuals who have above-average levels of a protein called SFRP4 in the blood are five times more likely to develop diabetes in the next few years than those with below-average levels", says Dr. Anders Rosengren, a researcher at the Lund University Diabetes Centre (LUDC), who has led the work on the risk marker. It is the first time a link has been established between the protein SFRP4, which plays a role in inflammatory processes in the body, and the risk of type 2 diabetes. Studies at the LUDC, in which donated insulin-producing beta cells from diabetic individuals and non-diabetic individuals have been compared, show that cells from diabetics have significantly higher levels of the protein. It is also the first time the link between inflammation in beta cells and diabetes has been proven. "The theory has been that low-grade chronic inflammation weakens the beta cells so that they are no longer able to secrete sufficient insulin. There are no doubt multiple reasons for the weakness, but the SFRP4 protein is one of them", says Dr. Taman Mahdi, main author of the study and one of the researchers in Dr. Rosengren's group. The level of the protein SFRP4 in the blood of non-diabetics was measured three times at intervals of three years.

November 5th

Inhibition of NOX4 Enzyme Prevents Liver Fibrosis

Researchers at the Bellvitge Biomedical Research Institute (IDIBELL) in Barcelona, Spain, have led a study published on September 26, 2012 in the online journal PLoS One showing that the inhibition of a family member of NADPH oxidase enzyme, NOX4, plays an important role in liver fibrosis. The researchers studied the function of a cytokine called transforming growth factor-beta (TGF-beta) in the pathophysiology of the liver, which is one of the main research lines of the Biological Clues of the Invasive and Metastatic Phenotype research group at the IDIBELL, led by Dr. Isabel Fabregat. This paper is related to the processes of liver fibrosis, an illness caused by the overproduction of extracellular matrix proteins in the liver tissue. During fibrosis, levels of TGF-beta are increased, and there is an activation of the extracellular matrix producing the activation of protecting cells of the extracellular matrix and other possible events leading to the death of hepatocytes. The TGF-beta is a complex cytokine. It is a prominent tumor suppressor in early stages of tumor formation, but, in advanced stages, the cells adapt to escape from the growth inhibitory signals and, under these conditions, the TGF-beta is able to potentiate tumor progression, contributing to metastasis. The study published in PLoS One is a collaboration between IDIBELL and the research group of Dr. Wolfgang Mikulits, co-author of the study, at the Cancer Research Institute of the Medical University of Vienna (Austria), that has provided cellular and animal models. The analysis in patient samples has been possible thanks to the collaboration with the University Hospital Alcorcon Foundation and the Complutense University of Madrid.