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Archive - Feb 19, 2015

Study in Myanmar Confirms Artemisinin-Resistant Malaria Close to Border with India

The spread of malaria parasites that are resistant to the drug artemisinin, the front-line treatment against malaria infection, into neighboring India would pose a serious threat to the global control and eradication of malaria. If drug resistance spreads from Asia to the African sub-continent, or emerges in Africa independently as we've seen several times before, millions of lives will be at risk. The collection of samples from across Myanmar and its border regions was led by Dr. Kyaw Myo Tun of the Defense Services Medical Research Centre, Napyitaw, Myanmar and coordinated by the Mahidol-Oxford Tropical Medicine Research Unit (MORU) in Bangkok, Thailand. The researchers examined whether parasite samples collected at 55 malaria treatment centres across Myanmar carried mutations in specific regions of the parasite's kelch gene (K13), a known genetic marker of artemisinin drug resistance. The team confirmed resistant parasites in Homalin, Sagaing Region located only 25 kilometers from the Indian border. The article describing these findings is to be published online on February 20, 2015 in Lancet Infectious Diseases. The article is titled “Spread of Artemisinin-Resistant Plasmodium falciparum in Myanmar: a Cross-Sectional Survey of the K13 Molecular Marker. "Myanmar is considered the front line in the battle against artemisinin resistance as it forms a gateway for resistance to spread to the rest of the world," says Dr. Charles Woodrow from the Mahidol-Oxford Tropical Medicine Research Unit and senior author of the current study at Oxford University. "With artemisinins we are in the unusual position of having molecular markers for resistance before resistance has spread globally.

Karolinska Scientists Use Single-Cell RNA-Seq Analysis to Map and Identify 47 Different Types of Cell in the Brain

Using a process known as single-cell sequencing, scientists at Karolinska Institutet have produced a detailed map of cortical cell types and the genes active within them. The study, which was published online on February 19, 2015 in Science, marks the first time this method of analysis has been used on such a large scale on such complex tissue. The article was titled “Cell Types in the Mouse Cortex and Hippocampus Revealed by Single-Cell RNA-seq.” The team studied over three thousand cells, one at a time, and even managed to identify a number of hitherto unknown types. “If you compare the brain to a fruit salad, you could say that previous methods were like running the fruit through a blender and seeing what color juice you got from different parts of the brain,” says Dr. Sten Linnarsson, Senior Researcher in the Department of Medical Biochemistry and Biophysics. “But in recent years we’ve developed much more sensitive methods of analysis that allow us to see which genes are active in individual cells. This is like taking pieces of the fruit salad, examining them one by one and then sorting them into piles to see how many different kinds of fruit it contains, what they’re made up of, and how they interrelate.” The knowledge that all living organisms are built up of cells is almost 200 years old. Since the discovery was made by a group of 19th century German scientists, we have also learnt that the nature of a particular body tissue is determined by its constituent cells, which are, in turn, determined by which genes are active in their DNA. However, little is still known about how this happens in detail, especially as regards the brain, the body’s most complex organ.

Eylea Outperforms Avastin and Lucentis in Treatment of Diabetic Macular Edema (DME) When Vision Loss Is Moderate to Severe

Neil Bressler, M.D., a researcher from Johns Hopkins Medicine helped lead colleagues from across the country in a government-sponsored study by the Diabetic Retinopathy Clinical Research Network to discover that three drugs--Eylea, Avastin, and Lucentis, used to treat diabetic macular edema (DME) are all effective. They also discovered that Eylea outperformed the other two drugs when vision loss was moderate to severe. Prior to this study, which will be published in the Feb. 18 issue of the New England Journal of Medicine, it was not known how the efficacy or safety of the three drugs compared. The title of the article is “Aflibercept, Bevacizumab, or Ranibizumab for Diabetic Macular Edema.” "These findings will equip patients with the information they need to discuss with their doctors which drug to choose and will help guide protocols for clinicians using these drugs to treat patients with diabetic macular edema," says Dr. Bressler, past chair of the Diabetic Retinopathy Clinical Research Network and Director of the Retina Division at Johns Hopkins Medicine. There are nearly 750,000 people in the U.S. affected by diabetic macular edema, a diabetes-related eye disease that causes vision loss. About one-quarter of those people may have moderate to severe vision loss from diabetic macular edema when they see an ophthalmologist. In fact, it is a leading cause of vision loss in working-age Americans and is becoming a major global public health issue. Diabetic macular edema affects the area of the eye that is used for reading, driving, and watching television, all common functions of daily living.

In Largest ALS Exome Sequencing Study Ever, International ALS Consortium Identifies Gene (TBK1) Newly Associated with Sporadic ALS; Shines Spotlight on Inflammation and Autophagy Pathways

Using advanced DNA sequencing methods, researchers have identified a new gene that is associated with sporadic, as opposed to familial, amyotrophic lateral sclerosis (ALS), or Lou Gehrig's disease. ALS is a devastating neurodegenerative disorder that results in the loss of all voluntary movement and is fatal in the majority of cases. The next-generation genetic sequencing of the exomes (protein-coding portions) of 2,874 ALS patients and 6,405 controls represents the largest number of ALS patients to have been sequenced in a single study to date. Though much is known about the genetic underpinnings of familial ALS, only a handful of genes have been definitively linked to sporadic ALS, which accounts for approximately 90 percent of all ALS cases. The newly associated gene, called TBK1, plays a key role at the intersection of two essential cellular pathways: inflammation (a reaction to injury or infection) and autophagy (a cellular process involved in the removal of damaged cellular components). The new study, conducted by an international ALS consortium that includes scientists and clinicians from Columbia University Medical Center (CUMC), Biogen Idec, and the HudsonAlpha Institute for Biotechnology, was published online on February 19, 2015 in Science.

[BioQuick Editor’s Note: It is perhaps fitting that this major advance in the understanding of Lou Gehrig’s disease (ALS) was achieved, in part, by scientists and clinicians from Columbia, as the great Gehrig himself, a New York City native, attended and played baseball at Columbia before leaving as a junior and heading on to baseball immortality with the New York Yankees. See “Lou Gehrig: Columbia Legend and American Hero” on the web (http://www.columbia.edu/cu/alumni/Magazine/Fall2001/Gehrig.html).]

Luna Moth Uses Long Wing Tails to Undermine Sonar Locator of Attacking Bats

Rachel Nuwer, a freelancer writing for the Smithsonian web site recently, described some fascinating work that scientists had done to establish exactly how the large luna moth is able to fend off the attacks of sonar- directed bats. BioQuick was most impressed and provides much of Ms. Nuwer’s story here. “Animals have evolved countless ways to avoid being eaten, ranging from impeccable camouflage, to deadly venom, to fortress-like shells. Some even adopt a seemingly desperate, last-ditch method: distract predators into attacking a non-essential part of the body. Gaudy eyespots on butterflies and fish encourage predators to strike at the periphery of wings or fins, while some lizards’ bright tails can break off in a confused bird’s mouth. These tricks buy precious time for potential prey to escape their attackers. All of these tactics, however, rely on visual deception, so it would seem that predators using other sensory information would be immune to such strategies. Insect-eating bats, for one, rely on echolocation—sonar cries that bounce off objects—to locate and capture flying prey. Now, however, scientists have found that even echolocation can be fooled by expendable frills. Luna moths, the grandiose fairy queens of the North American Lepidoptera ball, can use their tails to divert bats’ attention away from their juicy, delicate bodies. When luna moths fly, two long frills on the ends of their chartreuse wings spin. According to an article published online on February xx, 2015 in PNAS, that elegant display can muddle bats' sonar and thwart a deadly attack."

In Bowel Cancer Study, ICR Scientists Use New Technique (Capture Hi-C) to Demonstrate Long-Range Cancer Risk Effects of DNA Looping and Single Nucleotide Variants in Gene Deserts

Single-letter genetic variations within parts of the genome once dismissed as “junk DNA” can increase cancer risk through wormhole-like effects on far-off genes, new research shows. Researchers have found that DNA sequences within “gene deserts,” so called because they are completely devoid of genes, can regulate gene activity elsewhere by forming DNA loops across relatively large distances. The study, led by scientists at The Institute of Cancer Research (ICR) (http://www.icr.ac.uk), London, helps solve a mystery about how genetic variations in parts of the genome that don't appear to be doing very much can increase cancer risk. Researchers developed a new technique to study the looping interactions and discovered that single-letter DNA variations linked to the development of bowel cancer were found in regions of the genome involved in DNA looping. Their study, published online on February 19, 2015, in Nature Communications, is the first to look comprehensively at these DNA interactions specifically in bowel cancer cells, and has implications for the study of other complex genetic diseases. The effort was funded by the EU, Cancer Research UK, Leukaemia & Lymphoma Research, and the ICR. The researchers developed a technique called Capture Hi-C to investigate long-range physical interactions between stretches of DNA. This allowed them to look at how specific areas of chromosomes interact physically in more detail than ever before. Previous techniques used to investigate long-range DNA interactions were not sensitive enough to produce definitive results. The researchers assessed 14 regions of DNA that contain single-letter variations previously linked to bowel cancer risk. They detected significant long-range interactions for all 14 regions, confirming their role in gene regulation.

Universtity of Geneva Results Dictate Diffferent View of Endocytosis Process

Cellular biology still harbors mysteries. Notably, there is no unequivocal explanation behind endocytosis, the biological process that allows exchanges between a cell and its environment. Two hypotheses prevail for explaining how the membrane caves in and forms transport vesicles: either the initial impetus is due to a scaffold-like structure which the soccer ball-shaped clathrin proteins build between themselves, or clathrin's role is minor, and it is other, “adaptor” proteins that exert pressure on the cell membrane until endocytosis begins. One recently completed study by the Faculty of Science at the University of Geneva (UNIGE) reconciles the two theories, suggesting that a balance between forces is present: clathrin proteins are only slightly more influential than the others, and it is a clever combination of physical mechanisms that contributes to creating favorable conditions for the deformation of the membrane. The findings and conclusions were published in Nature Communications In vitro procedures by researchers in UNIGE's Department of Biochemistry shed new light on the phenomenon of endocytosis, the biological cycle that takes place at the membrane level, and ends with the formation of the transport compartments necessary for external exchanges. During endocytosis, the cell membrane of eukaryotic organisms becomes deformed, puckering and caving in, creating vesicles for transporting elements such as ions, nutrients, and signals that are necessary for life. This compartment is deployed from the membrane towards the inside of the cell; its creation implies the use of much energy, and a significant physical force. Two hypotheses provide different explanations for the origins of this process.

Sleep Loss May Disrupt Fat Metabolism and Be Associated with Insulin Resistance and Increased Type 2 Diabetes Risk; Simply Getting Enough Sleep May Help Counter the Current Epidemics of Diabetes and Obesity

Lack of sleep can elevate levels of free fatty acids in the blood, accompanied by temporary pre-diabetic conditions in healthy young men, according to new research published online February 19, 2015, in Diabetologia, the journal of the European Association for the Study of Diabetes. The study, which is the first ever to examine the impact of sleep loss on 24-hour fatty acid levels in the blood, adds to emerging evidence that insufficient sleep, a highly prevalent condition in modern society--may disrupt fat metabolism and reduce the ability of insulin to regulate blood sugars. It suggests that something as simple as getting enough sleep could help counteract the current epidemics of diabetes and obesity. "At the population level, multiple studies have reported connections between restricted sleep, weight gain, and type 2 diabetes," said Esra Tasali (photo), M.D., Assistant Professor of Medicine at the University of Chicago and senior author of the study. "Experimental laboratory studies, like ours, help us unravel the mechanisms that may be responsible." The researchers found that after three nights of getting only four hours of sleep, blood levels of fatty acids, which usually peak and then recede overnight, remained elevated from about 4 a.m. to 9 a.m. As long as fatty acid levels remained high, the ability of insulin to regulate blood sugars was reduced. The results provide new insights into the connections, first described by University of Chicago researchers 15 years ago, between sleep loss, insulin resistance, and heightened risk of type 2 diabetes.

Plants Survive Mass Extinction Events Better Than Animals

At least five mass extinction events have profoundly changed the history of life on Earth. But a new study led by researchers at the University of Gothenburg in Sweden shows that plants have been very resilient to these catastrophic events. For over 400 million years, plants have played an essential role in almost all terrestrial environments and covered most of the world's surface. During this long history, many smaller and a few major periods of extinction severely affected Earth's ecosystems and its biodiversity. In the upcoming issue of the journal New Phytologist, the Gothenburg team reports its results based on analysis of more than 20,000 plant fossils with the aim to understand the effects of such dramatic events on plant diversity. The article is entitled “Revisiting the Origin and Diversification of Vascular Plants through a Comprehensive Bayesian Analysis of the Fossil Record.” The team’s findings show that mass extinction events had very different impacts among plant groups. Negative rates of diversification in plants (meaning that more species died out than new species were formed) were never sustained through long time periods. This indicates that, in general, plants have been particularly good at surviving and recovering through tough periods.
"In the plant kingdom, mass extinction events can be seen as opportunities for turnover leading to renewed biodiversity," says lead author Dr. Daniele Silvestro. Most striking were the results for the Cretaceous-Paleogene mass extinction, caused by the impact of an asteroid off the Mexican coast some 66 million years ago. This event had a great impact on the configuration of terrestrial habitats and led to the extinction of all dinosaurs except birds, but surprisingly, it had only limited effects on plant diversity.