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Archive - Jan 2017

January 9th

Drug Shown to Reduce New Attacks & Symptom Progression in Some Multiple Sclerosis Patients

In separate clinical trials, a drug called ocrelizumab has been shown to reduce new attacks in patients with relapsing remitting multiple sclerosis (MS), and also new symptom progression in primary progressive MS. Two studies conducted by an international team of researchers, which included Dr. Amit Bar-Or and Dr. Douglas Arnold from the Montreal Neurological Institute and Hospital of McGill University, have discovered that ocrelizumab can significantly reduce new attacks in patients with relapsing MS, as well as slow the progression of symptoms caused by primary progressive MS. In one study, 732 patients with primary progressive MS were randomized on a 2:1 ratio to receive either ocrelizumab, a humanized monoclonal antibody that depletes CD20+ B cells, or a placebo. The proportion of patients with 12-week confirmed disability progression was 39.3 per cent with the placebo versus 32.9 per cent with ocrelizumab. After 24 weeks, the proportion with confirmed disability progression was 35.7 per cent with placebo versus 29.6 per cent with ocrelizumab. By week 120, timed 25-foot walk worsened by 55.1 per cent for placebo versus 38.9 per cent for ocrelizumab. Patients given ocrelizumab were also found to have fewer new brain lesions and less brain volume loss than those given the placebo. Researchers also tested ocrelizumab in two separate studies of patients with relapsing remitting MS, one a group of 821 and the other 835. In both studies, patients were randomized on a 1:1 ratio to receive either ocrelizumab or an already established treatment for relapsing MS: subcutaneous interferon-beta, injected three times weekly. Compared to the placebo, relapse rates in patients given ocrelizumab were 46-per-cent lower in one study and 47-per-cent lower in the other.

Ottoline Leyser Honored with 2017 FEBS | EMBO Women in Science Award

According to an announcement issued on January 9, 2017, Dr. Ottoline Leyser (photo) has been named recipient of the 2017 FEBS|EMBO Women in Science Award. The award recognizes outstanding achievements of female researchers in the life sciences in the past five years. Dr. Leyser, who is Director of the Sainsbury Laboratory at Cambridge University, UK, receives the honor for her work on the evolutionary, developmental and biochemical mechanisms that enable plants to respond and adapt to environmental changes. “It’s a great honor to receive this award,” says Dr. Leyser. “It’s both a joy and a privilege to work in research science, especially in molecular biology, where technological advances are currently opening up so many opportunities for discovery. To make the most of these opportunities, science needs diversity, and initiatives like this award have an important part to play in opening the doors of the laboratory to everyone." Professor Leyser’s focus on understanding how plants respond to their environment led to her discovery of the mechanism of action of the plant hormone auxin and the identification of a second group of plant hormones known as strigolactones. She has formulated a model of how the two hormone systems interact to regulate plant development. Her current work aims to elucidate the mechanisms underlying this model. In order to tackle this question, she has added computational modelling to the more traditional array of techniques used to study this complex system. Dr. Leyser is also an outstanding role model for future generations of researchers, having successfully combined academic research, parenthood, and other activities.

January 8th

Mediterranean Diet May Have Lasting Effects on Brain Health

A new study shows that older people who followed a Mediterranean diet retained more brain volume over a three-year period than those who did not follow the diet as closely. The study was published online on January 4, 2017 in Neurology®, the medical journal of the American Academy of Neurology. But contrary to earlier studies, eating more fish and less meat was not related to changes in the brain. The Mediterranean diet includes large amounts of fruits, vegetables, olive oil, beans and cereal grains such as wheat and rice, moderate amounts of fish, dairy and wine, and limited red meat and poultry. "As we age, the brain shrinks and we lose brain cells which can affect learning and memory," said study author Michelle Luciano, Ph.D., of the University of Edinburgh in Scotland. "This study adds to the body of evidence that suggests the Mediterranean diet has a positive impact on brain health." Researchers gathered information on the eating habits of 967 Scottish people around age 70 who did not have dementia. Of those people, 562 had an MRI brain scan at around age 73 to measure overall brain volume, gray matter volume, and thickness of the cortex, which is the outer layer of the brain. From that group, 401 people then returned for a second MRI at age 76. These measurements were compared to how closely participants followed the Mediterranean diet. The participants varied in how closely their dietary habits followed the Mediterranean diet principles. People who didn't follow as closely to the Mediterranean diet were more likely to have a higher loss of total brain volume over the three years than people who followed the diet more closely. The difference in diet explained 0.5 percent of the variation in total brain volume, an effect that was half the size of that due to normal aging.

3-D Antibody Arrays Offer Higher Sensitivity; New Tool May Help in Diagnosis of Malaria and Other Diseases

Exploiting a process known as molecular self-assembly, MIT chemical engineers have built three-dimensional arrays of antibodies that could be used as sensors to diagnose diseases such as malaria or tuberculosis. These sensors, which contain up to 100 stacked layers of antibodies, offer much more sensitivity than existing antibody-based sensors, which have only a single layer of antibodies. “The more antibodies you put on a surface, the lower the concentration of molecules you can detect,” says Bradley Olsen, Ph.D., an Associate Professor of Chemical Engineering at MIT. “You can have a big impact on biosensors by potentially improving the sensitivity by several orders of magnitude.” Dr. Olsen is the senior author of the study, which was published online on December 28, 2016 in the journal Angewandte Chemie. The paper’s lead author is MIT postdoc Xue-Hui Dong, and former postdoc Allie Obermeyer is also an author. The article is titled “Three-Dimensional Ordered Antibody Arrays Through Self-Assembly of Antibody–Polymer Conjugates.” The team’s new design approach relies on a phenomenon known as self-assembly, which occurs when thermodynamic interactions drive molecular building blocks to take on certain configurations. In this case, the researchers discovered that they could force antibodies and other proteins to form layers by attaching each protein to a polymer tail. The proteins and polymers repel each other, so the molecules arrange themselves in a structure that minimizes the interactions between the protein and polymer segments. “Because the protein and polymer are bonded together, they can’t separate like oil and water. They can only get apart from each other by a distance about the size of one molecule,” Olsen says.

How the Fruit Fly Brain Differentiates Between Self-Generated Visual Movement and Externally Generated Visual Movement

What you see is not always what you get. And that, researchers at The Rockefeller University have discovered, is a good thing. “Every time you move your eye, the whole world moves on your retina,” says Gaby Maimon, Ph.D., Head of the Laboratory of Integrative Brain Function at Rockefeller. “But you don’t perceive an earthquake happening several times a second.” By measuring electrical activity in individual neurons, scientists have discovered that a fly’s brain can cancel out misleading visual signals, effectively blinding the insect to sensory information that would otherwise interfere with its ability to turn while flying. That’s because the brain can tell if visual motion is self-generated, canceling out information that would otherwise make us feel—and act—as if the world was whirling around us. It’s an astonishing bit of neural computation—one that Dr. Maimon and his team are attempting to decode in fruit flies. And the results of their most recent investigations, published in Cell on January 5, 2015 provide fresh insights into how the brain processes visual information to control behavior. The article is titled “Quantitative Predictions Orchestrate Visual Signaling in Drosophila.” Each time you shift your gaze (and you do so several times a second), the brain sends a command to the eyes to move. But a copy of that command is issued internally to the brain’s own visual system, as well. This allows the brain to predict that it is about to receive a flood of visual information resulting from the body’s own movement—and to compensate for it by suppressing or enhancing the activity of particular neurons.

Scientists Increase Cas9-Based Bacterial Memories of Viruses by 100 Fold

Some microbes can form memories—although, inconveniently for scientists who study the process, they don’t do it very often. Rockefeller University researchers and colleagues at the University of California, Berkeley, have found a way to make bacteria encode memories much more frequently. Their discovery was published in the January 5, 2016 issue Molecular Cell. The article is titled “Mutations in Cas9 Enhance the Rate of Acquisition of Viral Spacer Sequences during the CRISPR-Cas Immune Response.” “CRISPR, the adaptive immune system found within many bacteria, remembers viruses by storing snippets of their DNA. But in nature, these recording events happen only rarely,” says senior author Luciano Marraffini, Ph.D., Head of the Laboratory of Bacteriology at Rockefeller. “We have identified a single mutation that causes bacterial cells to acquire genetic memories of viruses 100 times more frequently than they do naturally,” he adds. “This mutation provides a powerful tool for experiments in our lab and elsewhere, and could facilitate the creation of DNA-based data storage devices.” If a virus that a bacterium’s CRISPR system has recorded shows up again, an enzyme known as Cas9 (image) is dispatched to destroy it. The system’s precision has already made it an important tool for editing genomes, and scientists are looking toward other potential applications. For the current study, the team randomly introduced mutations into the gene for Cas9 and found that one of them prompts bacteria to acquire genetic memories more readily. Under normal conditions, if researchers expose 100,000 bacterial cells to the same potentially deadly virus, only one will typically acquire a DNA snippet that could enable it to survive a future attack.

January 7th

Study Characterizes Key Molecular Tool in DNA Repair Enzymes

New research has revealed the function of a widely shared enzyme component, the Zf-GRF domain, as a critical molecular tool necessary for manipulating DNA during repair processes. A living organism's DNA needs constant maintenance. Every cell is in a state of fierce siege, as plentiful reactive oxygen compounds and ions constantly assault and damage the cell's organic molecules, especially its DNA. Oxidative damage to DNA is estimated to occur 10,000 times per day per cell. In order for life to survive this molecular battlefield, molecular countermeasures have evolved, among them a suite of complex molecules that detect oxidative damage to sections of DNA molecules, targeting those areas with various repair molecules that perform a series of elaborate molecular engineering operations necessary to fix the problem. The intimate mechanics of the complex molecular assemblies dedicated to the recognition, repair and signaling of DNA damage are still not fully understood. A specific protein structure known as the Zf-GRF domain is a mysterious component of APE2, a DNA-repair and DNA damage response enzyme, and is also common to a number of other DNA-maintaining molecules. A new research finding shows that Zf-GRF performs a critical DNA binding function in helping enzymes properly align to single-stranded DNA. The new study appears in a paper published online in PNAS on December 27, 2016. The article is titled "APE2 Zf-GRF Facilitates 3'-5' Resection of DNA Damage Following Oxidative Stress.” The finding is a result of two teams, one headed by Shan Yan from the Department of Biological Sciences at the University of North Carolina at Charlotte and the second headed by R.

Biomarker Signatures of Aging

Levels of specific biomarkers found in the blood can be combined to produce patterns that signify how well a person is aging and his or her risk for future aging-related diseases, according to a new study by researchers at the Boston University Schools of Public Health and Medicine and Boston Medical Center. The study, which was published online on January 6, 2016 in the journal Aging Cell, used biomarker data collected from the blood samples of almost 5,000 participants in the Long Life Family Study, funded by the National Institute on Aging (NIA) at the National Institutes of Health (NIH). The open-access article is titled “Biomarker Signatures of Aging.” The researchers found that a large number of people--about half --had an average "signature," or pattern, of 19 biomarkers. But smaller groups of people had specific patterns of those biomarkers that deviated from the norm and that were associated with increased probabilities of association with particular medical conditions, levels of physical function, and mortality risk eight years later. For example, one pattern was associated with disease-free aging, another with dementia, and another with disability-free aging in the presence of cardiovascular disease. In all, the researchers generated 26 different predictive biomarker signatures. Instances where similar biomarker data were available from the long-running Framingham Heart Study allowed for about one-third of the signatures to be replicated. "These signatures depict differences in how people age, and they show promise in predicting healthy aging, changes in cognitive and physical function, survival, and age-related diseases like heart disease, stroke, type 2 diabetes, and cancer," the authors said.

January 6th

Elevated Levels of Tau Protein Associated with Longer Recovery from Concussion

Elevated levels of the brain protein tau following a sport-related concussion are associated with a longer recovery period and delayed return to play for athletes, according to a study published online on January 6, 2017 in Neurology®, the medical journal of the American Academy of Neurology. The findings suggest that tau, which can be measured in the blood, may serve as a marker to help physicians determine an athlete's readiness to return to the game. The article is titled “Acute Plasma Tau Relates to Prolonged Return to Play After Concussion.” Despite the 3.8 million sports-related concussions that occur annually in the United States, there are no objective tools to confirm when an athlete is ready to resume play. Returning to play too early, before the brain has healed, increases an athlete's risk of long-term physical and cognitive problems, especially if he or she sustains another concussion. Currently, physicians and trainers must make return-to-play decisions based on an athlete's subjective, self-reported symptoms and their performance on standardized tests of memory and attention. A team led by Jessica Gill, R.N., Ph.D. of the National Institute of Nursing Research at the National Institutes of Health and Jeffrey Bazarian, M.D., M.P.H. of the University of Rochester Medical Center evaluated changes in tau in 46 Division I and III college athletes who experienced a concussion. Tau, which plays a role in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia, and Alzheimer's disease was measured in preseason blood samples and again within 6 hours following concussion using an ultra-sensitive technology that allows researchers to detect single protein molecules.

Research Reveals How Bacteria Resist “Last-Resort” Antibiotic

An international research team, led by the University of Bristo (UK), has provided the first clues to understand how the mcr-1 gene protects bacteria from colistin - a 'last resort' antibiotic used to treat life-threatening bacterial infections that do not respond to other treatment options. Last year, members of the team, led by Dr. Jim Spencer from the School of Cellular and Molecular Medicine, in collaboration with colleagues from Oxford, Cardiff, Diamond Light Source, Thailand, and China, identified mcr-1 as the first colistin-resistance gene that could be passed between bacteria, enabling resistance to spread rapidly within a bacterial population. Since then, the mcr-1 gene has been detected in common bacteria, such as E. coli, in China, the United States, and across Europe, first in farm animals and recently - worryingly - in human patients. The spread of mcr-1 has been linked to agricultural use of colistin, indicating that transmission between animals and humans may take place. In response to these findings the Chinese government has now banned use of colistin in animal feed. Colistin acts by binding to, and disrupting, the outer surface of bacteria. Bacteria carrying the mcr-1 gene make a protein that modifies the bacterial surface to reduce colistin binding, making the organism resistant. In its work, the team used X-rays produced at Diamond's crystallography beamlines to generate detailed pictures of the portion of this protein responsible for this modification, and with this information identified key features that are necessary for it to function. They also constructed computer models of the chemical reaction that leads to resistance.