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Archive - Jan 27, 2014

Hopkins Study Suggests Non-CpG Methylation Is Reversible System of Gene Regulation That May Contribute to Rett Syndrome

In normal development, all cells turn off genes they don't need, often by attaching a chemical methyl group to the DNA, a process called methylation. Historically, scientists believed methyl groups could only stick to a particular DNA sequence: a cytosine followed by a guanine, called CpG. But in recent years, methyl groups have been found on other sequences, and so-called non-CpG methylation has been found in stem cells, and in neurons in the brain. Now, a team of researchers at Johns Hopkins has discovered that non-CpG methylation occurs later and more dynamically in neurons than previously appreciated, and that it acts as a system of gene regulation, which can be independent of traditional CpG methylation. In a study that was published online on December 23, 2013 in Nature Neuroscience, the Hopkins team describes this new gene control mechanism and how it may contribute to Rett Syndrome, a nervous system disorder affecting mostly girls that causes problems with movement and communication. The research team, led by Hongjun Song, Ph.D., professor of neurology and director of Johns Hopkins Medicine's Institute for Cell Engineering's Stem Cell Program, had found non-CpG methylation prevalent in neurons, a finding that surprised the team, because this wasn't found in any other cells other than stem cells. By looking at what genes were being transcribed in neurons, he and his colleagues found that, like the form of methylation scientists had seen in stem cells, non-CpG methylation stops genes from being expressed. They also mapped the genome to find where non-CpG methylation happens, and found that it carves out its own niche, and the sites are distributed in regions without CpG methlyation. "That was the first hint that maybe it can function independently of CpG methylation," Dr. Song says.

Study Casts Doubt on Theory That Retired NFL Football Players Suffer Chronic Traumatic Encephalopathy (CTE)

The media have widely reported that a debilitating neurological condition called chronic traumatic encephalopathy (CTE) is a well-established disease in retired athletes who played football and other contact sports. But a study by a Loyola University Medical Center neuropsychologist has found little evidence that CTE actually exists. "There has not yet been one controlled epidemiological study looking at the risk of late-life cognitive impairment in any collision sport, including boxing, American football, or other sports involving repetitive head trauma," Christopher Randolph, Ph.D., reports in an open-access article in the January-February 2014 peer-reviewed journal Current Sports Medicine Reports. The author declares no conflict of interest and has no financial disclosures. CTE is said to be the cause of behavioral symptoms such as anger, aggression and suicidality, and cognitive symptoms such as impaired learning and memory problems. CTE is thought to be linked to concussions and characterized by the build-up of abnormal substances in the brain called tau proteins. A 2005 study, co-authored by Dr. Randolph, reported that rates of mild cognitive impairment among retired National Football League (NFL) players seemed to be higher than that of the general population, but Dr. Randolph noted there were no controls in this study, and results may have been subject to reporting biasb A more recent study of retired NFL players found that rates of Alzheimer's disease and amyotrophic lateral sclerosis (ALS or Lou Gehrig's disease) were higher than that of the general population. But this may be due to the fact that the NFL players had lower overall mortality rates from heart disease and other causes. Because they lived longer, the players naturally would be more likely to get age-related diseases such as Alzheimer's disease.

DNA-Glued Gold Nanostructures Safely Target and Image Cancerous Tumors

A team of researchers at the University of Toronto has discovered a method of assembling "building blocks" of gold nanoparticles as the vehicle to deliver cancer medications or cancer-identifying markers directly into cancerous tumors. The study, led by Dr. Warren Chan, Professor at the Institute of Biomaterials & Biomedical Engineering (IBBME) and the Donnelly Centre for Cellular & Biomolecular Research (CCBR), appears in an article published online on January 27, 2014 in Nature Nanotechnology. "To get materials into a tumor they need to be a certain size," explains Dr. Chan. "Tumors are characterized by leaky vessels with holes roughly 50 – 500 nanometers in size, depending on the tumor type and stage. The goal is to deliver particles small enough to get through the holes and 'hang out' in the tumor's space for the particles to treat or image the cancer. If a particle is too large, it can't get in, but if the particle is too small, it leaves the tumor very quickly." Dr. Chan and his fellow researchers solved this problem by creating modular structures 'glued' together with DNA. "We're using a 'molecular assembly' model - taking pieces of materials that we can now fabricate accurately and organizing them into precise architectures, like putting LEGO blocks together," comments Leo Chou, a 5th year Ph.D. student at IBBME and first author of the paper. Dr. Chou was awarded a 2012-13 Canadian Breast Cancer Foundation Ontario Region Fellowship for his work with nanotechnology. "The major advantage of this design strategy is that it is highly modular, which allows you to 'swap' components in and out. This makes it very easy to create systems with multiple functions, or screen a large library of nanostructures for desirable biological behaviors," he states.