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Archive - Feb 18, 2017

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Powerful Optical Imaging Technology (SICLON) Resolves Natural Fluorescence of DNA

Many of the secrets of cancer and other diseases lie in the cell's nucleus. But getting way down to that level -- to see and investigate the important genetic material housed there -- requires creative thinking and extremely powerful imaging techniques. Dr. Vadim Backman and Dr. Hao Zhang, nanoscale imaging experts at Northwestern University, have developed a new imaging technology that is the first to see DNA "blink," or fluoresce. The tool enables the researchers to study individual biomolecules as well as important global patterns of gene expression, which could yield insights into cancer. Dr. Backman was to discuss the tool and its applications -- including the new concept of macrogenomics, a technology that aims to regulate the global patterns of gene expression without gene editing – on Friday (February 17, 2017) at the American Association for the Advancement of Science (AAAS) annual meeting in Boston. The talk, entitled "Label-Free Super-Resolution Imaging of Chromatin Structure and Dynamics," is part of the symposium "Optical Nanoscale Imaging: Unraveling the Chromatin Structure-Function Relationship," which was to be held from 1 to 2:30 p.m. Eastern Time February 17 in Room 206, Hynes Convention Center. The Northwestern tool features six-nanometer resolution and is the first to break the 10-nanometer resolution threshold. It tool image DNA, chromatin, and proteins in cells in their native states, without the need for labels. For decades, textbooks have stated that macromolecules within living cells, such as DNA, RNA and proteins, do not have visible fluorescence on their own. "People have overlooked this natural effect because they didn't question conventional wisdom," said Dr. Backman, the Walter Dill Professor of Biomedical Engineering in the McCormick School of Engineering at Northwestern.

Gene Expression in Fetal Spine Key to the Development of Hemispheric Asymmetries Associated with Handedness

A preference for the left or the right hand might be traced back to that asymmetry. "These results fundamentally change our understanding of the cause of hemispheric asymmetries," conclude the authors. The team reported about their study on February 1, 2017 in the journal eLife. The article is titled “Epigenetic Regulation of Lateralized Fetal Spinal Gene Expression Underlies Hemispheric Asymmetries.” “Epigenetic regulation of lateralized fetal spinal gene expression underlies hemispheric asymmetries.” To date, it had been assumed that differences in gene activity of the right and left hemisphere might be responsible for a person's handedness. A preference for moving the left or right hand develops in the womb from the eighth week of pregnancy, according to ultrasound scans carried out in the 1980s. From the 13th week of pregnancy, unborn children prefer to suck either their right or their left thumb. Arm and hand movements are initiated via the motor cortex in the brain. It sends a corresponding signal to the spinal cord, which in turn translates the command into a motion. The motor cortex, however, is not connected to the spinal cord from the beginning. Even before the connection forms, precursors of handedness become apparent. This is why the researchers have assumed that the cause of right respective left preference must be rooted in the spinal cord rather than in the brain. The researchers analyzed the gene expression in the spinal cord during the eighth to twelfth week of pregnancy and detected marked right-left differences in the eighth week -- in precisely those spinal cord segments that control the movements of arms and legs. Another study had shown that unborn children carry out asymmetric hand movements just as early as that.

Intriguing Dance Revealed Among Interacting Herbivores, Plants, and Microbes

What looks like a caterpillar chewing on a leaf or a beetle consuming fruit is likely a three-way battle that benefits most, if not all of the players involved, according to a Penn State entomologist. "Plants are subject to attack by an onslaught of microbes and herbivores, yet are able to specifically perceive the threat and mount appropriate defenses," said Gary W. Felton, Ph.D., Professor and Head of Entomology. "But, herbivores can evade plant defenses by using symbiotic bacteria that deceive the plant into perceiving a herbivore threat as microbial, suppressing the plant's defenses against herbivores." Dr. Felton's research looked at two crop pests -- tomato fruit worms and the Colorado potato beetle -- plant reactions to the pests, and the microbes that they carry. He presented his findings on February 18, 2017 at the annual meeting of the American Association for the Advancement of Science (AAAS) in Boston. This broad look at herbivore-plant interactions takes into account the entire phytobiome -- the plants, their environment, their predators, and the organisms that colonize them. Tomato fruit worms may be the most important crop pest in North and South America. According to Dr. Felton, the caterpillar enjoys eating more than 100 different agricultural crops. Unfortunately, it likes to eat what we humans eat. The Colorado potato beetle moved quickly across the U.S. from Mexico in the mid-1800s and took only 20 to 30 years to reach New York and Long Island. It strips leaves down to the veins, leaving skeletal remains. Plants have two lines of defense against these predators. One reaction, regulated by jasmonic acid, comes into play when insects chew on the plant's leaves, stems or fruit, damaging the plant and leaving insect saliva.

Scientists ID Molecule That Can Robustly Inhibit Nonsense-Mediated Decay of RNA; May Ultimately Offer Avenue to Treatment of ALS, Muscular Dystrophy, and Cystic Fibrosis

In cells, DNA is first converted to RNA, and RNA is next converted to proteins--a complicated process involving several other steps. Nonsense-mediated RNA decay (NMD) is a processing pathway in cells that, like a broom, cleans up erroneous RNA to prevent its productive conversion into an aberrant protein, which could lead to disease. In some diseases, like amyotrophic lateral sclerosis (ALS, also called Lou Gehrig's disease), excessive junk RNA is produced, possibly contributing to the disease. In such instances, more NMD is useful to get rid of the junk RNA. In other diseases, such as muscular dystrophy and cystic fibrosis, a decrease in NMD is a better option. In these diseases, the NMD pathway eliminates the RNA, resulting in a complete loss of the gene function. But a defective RNA may translate to a semi-functional protein, which is better than no RNA for protein formation in cells. And so, a tuned-down NMD is more useful. Dr. Sika Zheng, an Assistant Professor of Biomedical Sciences in the School of Medicine at the University of California, Riverside, and colleagues now report in the journal RNA (volume 23, no.3, March 2017 issue) that they have come up with a method in the lab that detects NMD efficiency inside the cell. The article is titled “Inhibition of Nonsense-Mediated RNA Decay by ER Stress.” "Our method can screen a host of chemicals and allows us to identify molecules that regulate this efficiency," Dr. Zheng said. "We have already identified thapsigargin as a molecule that indirectly and robustly inhibits NMD." The new method works by harnessing some normal targets of NMD and turning them into "reporters" of NMD activity. The method relies on the knowledge that NMD is more than a quality-control mechanism; it can also determine the level of some naturally occurring RNA.

Adjusting Levels of Kynurenic Acid Can Have Significant Effects on Schizophrenic-Like Behavior in Mice

A new study by University of Maryland School of Medicine researchers, and collaborators, has found that in mice, adjusting levels of a compound called kynurenic acid can have significant effects on schizophrenia-like behavior. The study was published online on December 16, 2016 in Biological Psychiatry. The article is titled “Adaptive and Behavioral Changes in Kynurenine 3-Monooxygenase Knockout Mice: Relevance to Psychotic Disorders.” In recent years, scientists have identified kynurenic acid as a potential key player in schizophrenia. People with schizophrenia have higher than normal levels of kynurenic acid in their brains. KYNA, as it is known, is a metabolite of the amino acid tryptophan; it decreases glutamate, and research has found that people with this schizophrenia tend to have less glutamate signaling than people without chizophrenia. Scientists have theorized that this reduction in glutamate activity, and therefore the higher KYNA levels seen in patients, might be connected with a range of symptoms seen in schizophrenia, especially cognitive problems. For several years, Robert Schwarcz, Ph.D., a Professor in the Department of Psychiatry at the University of Maryland School of Medicine (UM SOM), who in 1988 was the first to identify the presence of KYNA in the brain, has studied the role of KYNA in schizophrenia and other neuropsychiatric diseases. For the new study, Dr. Schwarcz and his team collaborated closely with scientists at the Karolinska Institute in Stockholm, Sweden, the University of Leicester in the United Kingdom, and KynuRex, a biotech company in San Francisco. "This study provides crucial new support for our longstanding hypothesis," Dr. Schwarcz said. "It explains how the KYNA system may become dysfunctional in schizophrenia."