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Archive - 2014

January 15th

Single Cell Sequencing Chosen 2013 Method of the Year by Nature Methods

The journal Nature Methods has selected single cell sequencing as the “Method of the Year” for 2013. In an editorial published on December 30, 2013, editors of Nature Methods said, “Once considered a technical challenge reserved for a few specialized labs, single-cell transcriptome and genome sequencing is becoming robust and broadly accessible. Exciting insights from recent studies are revealing the potential to understand biology at the unitary resolution of life, and last year marked a turning point in the widespread adoption of these methods to address a variety of research questions. For these reasons, single-cell sequencing is our choice of Method of the Year for 2013.” The journal presents a host of commentaries on different aspects of this exciting methodology. The journal outlines basic workflows and considerations in a Primer and describes currently useful applications in a News Feature. One Commentary describes how the method can be used to determine recombination frequencies, while a second suggests that single-cell transcriptome sequencing will deepen our understanding of gene regulation. A third Commentary discusses directions that complementary technologies must take to understand single cells at the level of function. Finally, the journal provides a section on Methods to Watch as we head into the future. This section can be found in the Method of the Year packet of information.

Beetle Study Shows Mitochondrial Genes Important for Survival and Reproduction

Contrary to common belief, mitochondrial genes seem to matter for how well individuals survive and reproduce. These new results are reported by researchers at Uppsala University who studied the genes of a common beetle species. Mitochondria are vital power plants of cells. They carry their own genes, which are inherited only through females, and these genes vary greatly between individuals. In the January 2014 issue of the prestigious scientific journal Ecology Letters, researchers from Uppsala University show for the first time that differences in the mitochondrial genes that individuals carry actually affect how well they survive and reproduce. It took the researchers two years to conduct the experiments, where they followed 180 populations of the seed beetle Callosobruchus maculatus (image) for more than 10 generations. The study was financed by the European Research Council and the Swedish Research Council and the results are based on gene sequence data from more than 2000 individuals. Remarkably, the authors found that individuals who carried rare mitochondrial genes were consistently those who did best. "This provides an explanation for why genetic variation is maintained. Much like a pendulum of a clock will never stop in either of the extreme sideway positions," says Professor Göran Arnqvist, one of the authors of the study. For decades, much biological research has rested on the assumption that different variants of the same mitochondrial gene are equivalent in terms of function of the gene. These genes have therefore been extensively used as a neutral "markers" that allow, for example, determination of the size of populations or reconstructions of the history of immigration into an area.

Gold Nanoparticles Key to New Virus-Tracking Method

Researchers at the Nanoscience Center (NSC) of University of Jyväskylä in Finland have developed a novel method to study enterovirus structures and their functions. The method will help to obtain new information on trafficking of viruses in cells and tissues as well as on the mechanisms of virus opening inside cells. This new information is important, for example, for developing new antiviral drugs and vaccines. The study was published online on January 13, 2014 in PNAS. The research was funded by the Academy of Finland and the TEKES FiDiPro -project NOVAC (Novel methods for vaccination and virus detection). Enteroviruses are pathogenic viruses infecting humans. This group consists of polioviruses, coxsackieviruses, echoviruses, and rhinoviruses. Enteroviruses are the most common causes of flu, but they also cause serious symptoms such as heart muscle infections and paralysis. Recently, enteroviruses have also been linked with chronic diseases such as diabetes. The infection mechanisms and infectious pathways of enteroviruses are still rather poorly understood. Previous studies in the group of Dr. Varpu Marjomäki at the NSC have focused on the cellular factors that are important for the infection caused by selected enteroviruses. The mechanistic understanding of virus opening and the release of the viral genome in cellular structures for starting new virus production is still largely lacking. Furthermore, the knowledge of infectious processes in tissues is hampered by the lack of reliable tools for detecting virus infection. The newly developed method involves a chemical modification of a known thiol-stabilized gold nanoparticle, the so-called Au102 cluster that was first synthesized and structurally solved by the group of Dr.

January 13th

New Discovery Could Stimulate Plant Growth and Increase Crop Yields

Scientists led by experts at Durham University in the UK have discovered a natural mechanism in plants that could stimulate their growth even under stress and potentially lead to better crop yields. Plants naturally slow their growth or even stop growing altogether in response to adverse conditions, such as water shortage or high salt content in soil, in order to save energy. They do this by making proteins that repress the growth of the plant. This process is reversed when plants produce a hormone - called gibberellin - which breaks down the proteins that repress growth. Growth repression can be problematic for farmers as crops that suffer from restricted growth produce smaller yields The research team, led by the Durham Centre for Crop Improvement Technology, and including experts at the University of Nottingham, Rothamsted Research. and the University of Warwick, have discovered that plants have the natural ability to regulate their growth independently of gibberellin, particularly during times of environmental stress. The scientists found that plants produce a modifier protein, called SUMO that interacts with the growth-repressing proteins. The researchers believe that by modifying the interaction between the modifier protein and the repressor proteins they can remove the brakes from plant growth, leading to higher yields, even when plants are experiencing stress. The interaction between the proteins can be modified in a number of ways, including by conventional plant breeding methods and by biotechnology techniques. The research was carried out on Thale Cress, a model for plant research that occurs naturally throughout most of Europe and Central Asia, but the scientists say the mechanism they have found also exists in crops such as barley, corn, rice, and wheat. Corresponding author Dr.

Possible Help for Migraine Sufferers

Candesartan is just as effective as the more commonly prescribed propranolol when it comes to preventing migraine attacks, according to a new study from St. Olavs Hospital in Trondheim, Norway and the Norwegian University of Science and Technology (NTNU), which was published online on December 11, 2013 in the journal Cephalalgia. The researchers have also found that candesartan may work for patients who get no relief from propranolol. "This gives doctors more possibilities and we can help more people," says Professor Lars Jacob Stovner, leader of Norwegian National Headache Centre, who also led the study. If one drug doesn't work for the migraine patient, the other one may. Side effects may also vary from patient to patient. The new study is a follow-up on a ten-year-old study from the NTNU. Candesartan is already in use by several doctors as a migraine prophylactic, but the NTNU follow-up study, which confirms the study from a decade ago, provides the proof that the drug actually works. More than 20 percent of migraine patients report that they feel better even when they are given a placebo. But blind tests show that candesartan works preventively for another 20 to 30 percent of patients. The hope now is that candesartan will be even more commonly prescribed. Migraines are thought to affect a staggering one billion people worldwide. Twelve percent of the Norwegian population suffers from migraines, or more than 500,000 individuals. This poses problems for the individual, but is also costly for society in the form of sick leave and reduced ability to work. Preventing migraines thus offers many benefits. The NTNU study was a triple-blind test, which means that neither patients nor doctors nor those who analyzed the results knew whether the patients had been given placebo or real medicine, Dr. Stovner said.

Two Sources of Reactive Oxygen Appear Required in Diabetic Retinopathy

The retina can be bombarded by reactive oxygen species in diabetes, prompting events that destroy healthy blood vessels, form leaky new ones, and ruin vision. Now researchers have learned that those chemically reactive molecules must come from both the bone marrow as well as the retinal cells themselves to cause such serious consequences. "It's a cascade that requires two players to signal the next event that causes the damage," said Dr. Ruth Caldwell, cell biologist at the Vascular Biology Center at the Medical College of Georgia (MCG) at Georgia Regents University. The good news is the finding also provides two new points for intervention, said Dr. Modesto Rojas, MCG postdoctoral fellow and first author of the study published online on December 17, 2013 in the open-access journal PLOS ONE. Excessive glucose in the blood prompts excessive production of reactive oxygen species, or ROS, and the light-sensitive retina is particularly vulnerable. Dr. Caldwell's research team had previously documented that ROS from white blood cells produced by the bone marrow as well as from retinal cells were the major instigators in diabetic retinopathy, a leading cause of blindness worldwide. But they weren't sure which mattered most. So they looked as several different scenarios, including mice lacking the ability to produce ROS by either the retinal or white blood cells, and found that if either were lacking, future damage was essentially eliminated. "One alone can't do it," said Dr. Caldwell, the study's corresponding author. "They did not develop the early signs of diabetic retinopathy that we were measuring." While blocking ROS production by retinal cells could be difficult, drugs already exist that reduce activation of white blood cells.

January 12th

Unique Molecular Tool Developed to Isolate mRNA from Single Live Cells

A multi-disciplinary team from the University of Pennsylvania (Penn) has published online on January 12, 2014 in Nature Methods a first-of-its-kind technique to isolate mRNA from live cells in their natural tissue microenvironment without damaging nearby cells. This allows the researchers to analyze how cell-to-cell chemical connections influence individual cell function and overall protein production. Tissues, of course, are complex structures composed of various cell types. The identity and function of individual cells within each tissue type – heart, skin, brain, for example -- are closely linked by which genes are transcribed into mRNA, and ultimately proteins. To study gene expression in single cells in their natural tissue setting, researchers must be able to look at a cell's inner workings, much as an ecologist does when studying how an individual species interacts with its habitat. Even cells of seemingly the same type are not identical at the molecular level. Most knowledge about variability in gene expression has been from studies using heterogeneous groups of cells grown in culture. Researchers doubt the ability to extrapolate "real biology" from these unnatural conditions. Tools for investigating what type and how much RNA is present in single cells in intact tissue provide a unique opportunity to assess how mammalian cells really work and how that function may go awry in various diseases, and eventually in testing new drugs. James Eberwine, Ph.D., professor of Pharmacology, Perelman School of Medicine, and co-director of the Penn Genome Frontiers Institute (PGFI), and Ivan Dmochowski, Ph.D., associate professor of Chemistry, School of Arts and Sciences, co-directed this study. Other Penn co-authors include Jai-Yoon Sul, Ph.D., assistant professor of Pharmacology,and M.

Non-Coding DNA Implicated in Type 2 Diabetes

Variations in non-coding sections of the genome might be important contributors to type 2 diabetes risk, according to a new study. DNA sequences that do not encode proteins were once dismissed as "junk DNA," but scientists are increasingly discovering that some such regions are important for controlling which genes are switched on. The new study, published online on January 12, 2014 in Nature Genetics, is one of the first to show how such regions, called regulatory elements, can influence people's risk of disease. Type 2 diabetes affects over 300 million people worldwide. Genetic factors have long been known to have an important role in determining a person's risk of type 2 diabetes, alongside other factors such as body weight, diet, and age. Many studies have identified regions of the genome where variations are linked to diabetes risk, but the function of many of these regions is unknown, making it difficult for scientists to glean insights into how and why the disease develops. Only approximately two per cent of the genome is made up of genes: the sequences that contain code for making proteins. Most of the remainder is shrouded in mystery. "Non-coding DNA, or junk DNA as it is sometimes known, is the dark matter of the genome. We're only just beginning to unravel what it does," said leading author Professor Jorge Ferrer, a Wellcome Trust Senior Investigator from the Department of Medicine at Imperial College London. In the new study, scientists mapped the regulatory elements that orchestrate gene activity in the cells of the pancreas that produce insulin. In type 2 diabetes, the tissues become less responsive to insulin, resulting in blood sugar levels being too high.

Targetable BRAF Mutation Found to Drive Rare Brain Tumor

Scientists have identified a mutated gene that causes a type of tenacious, benign brain tumor that can have devastating lifelong effects. Currently, the tumor can only be treated with challenging repeated surgeries and radiation. The discovery, reported online on January 12, 2014 in Nature Genetics, is encouraging, because it may be possible to attack the tumors with targeted drugs already in use for other kinds of tumors, said the investigators from Dana-Farber/Boston Children's Cancer and Blood Disorders Center, Massachusetts General Hospital (MGH), and the Broad Institute of MIT and Harvard. The mutated gene, known as BRAF, was found in almost all samples of tumors called papillary craniopharyngiomas. This is one of two types of craniopharyngiomas—the other being adamantinomatous—that develop in the base of the brain near the pituitary gland, hypothalamus, and optic nerves. The papillary craniopharyngiomas occur mainly in adults; adamantinomatous tumors generally affect children. The researchers identified a different mutant gene that drives the tumors in children. Drugs that target these adamantinomatous tumors are not yet clinically available, but may be in the future, said the researchers. "From a clinical perspective, identifying the BRAF mutation in the papillary tumors is really wonderful, because we have drugs that get into the brain and inhibit this pathway," said Sandro Santagata, M.D., Ph.D., a co-senior author of the paper. "Previously, there were no medical treatments—only surgery and radiation—and now we may be able to go from this discovery right to a well-established drug therapy." BRAF inhibitors are currently used in treating malignant melanoma when that BRAF mutation is present. Priscilla Brastianos, M.D., co-first author of the study, and Dr.

January 11th

Team Seeks Source of Body Louse Pathology for Humans

A new study seeks to determine how one parasitic species can give rise to two drastically different outcomes in its host: The human body louse (Pediculus humanus) can transmit dangerous bacterial infections to humans, while the human head louse (also Pediculus humanus) does not. A report of the new study as published online on January 9, 2014 in the journal Insect Molecular Biology. "Body louse-transmitted diseases include trench fever, relapsing fever, and epidemic typhus," said University of Illinois entomology professor Dr. Barry Pittendrigh, who led the research. In a previous study, Dr. Pittendrigh and his colleagues compared the sequences of all protein-coding genes in head and body lice and determined that the two belonged to the same species – despite the fact that body lice are bigger than head lice, cling to clothing instead of hair, and can transmit disease. Since the early 2000s, Dr. Pittendrigh has worked with Dr. John M. Clark, a professor of environmental toxicology and chemistry at the University of Massachusetts, on the molecular biology and genomics of lice. Dr. Clark was a collaborator on the 2012 study, and the two have had "a long-term goal of trying to solve this question of why body lice transmit bacterial diseases and head lice don't," Dr. Pittendrigh said. In the new study, Dr. Clark's group infected head and body lice with Bartonella quintana, the bacterium that causes trench fever. Dr. Pittendrigh's laboratory then looked at gene expression in each to see how the insects responded to the infection. "Our experiments suggest that the head louse immune system is fairly effective in fighting off the bacteria that cause trench fever," Dr. Pittendrigh said.