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Archive - Feb 2017

Date

February 19th

Synthetic Compound Developed at Moscow State University Slows Down Aging of Mice with Mutated Mitochondria

A group of Russian and Swedish scientists has recently published a breakthrough paper, reporting results of a joint study by Lomonosov Moscow State University and Stockholm university. The article was published in the U.S. journal Aging. The major goal of the study was to investigate the role of intracellular powerstations -- mitochondria -- in the process of aging of organisms. Importantly, scientists made an attempt to slow down aging using a novel compound: artificial antioxidant SkQ1 precisely targeted into mitochondria. This compound was developed at the Moscow State University by the most cited Russian biologist Professor Vladimir Skulachev. Experiments involved a special strain of genetically-modified mice created and characterized in Sweden. A single mutation was introduced into the genome of these mice resulting in the substantially accelerated mutagenesis in mitochondria. This leads to accelerated agiing and early death of the mutant mice. They live less than 1 year (normal mouse lives more than 2 years). The mutation promotes development of many age-related defects and diseases indicating that the major defect of these mice is indeed aging. Starting from the age of 100 days one group of mutant mice was treated with small doses of SkQ1 (approxamtely 12 micrograms) added into their drinking water. Per scientists' hypothesis, the compound must protect animal cells from the toxic byproducts of mitochondria -- free radicals (reactive oxygen species). Another group of animals served as a control group receiving pure water. Differences between the two groups became obvious starting from the age 200-250 days. Animals in the control group aged rapidly as expected.

Gene Editing Can Complement Traditional Food-Animal Improvements

Gene editing -- one of the newest and most promising tools of biotechnology -- enables animal breeders to make beneficial genetic changes, without bringing along unwanted genetic changes. And, following in the footsteps of traditional breeding, gene editing has tremendous potential to boost the sustainability of livestock production, while also enhancing food-animal health and welfare, argues University of California (UC) Davis animal scientist Dr. Alison Van Eenennaam. She examined the potential benefits of genome editing on Friday, February 17, 2017 at the annual meeting of the American Association for the Advancement of Science, to be held in Boston's Hynes Convention Center. Her presentation was part of a 3 p.m. EST session titled "The Potential of Gene Editing to Revolutionize Agriculture," moderated by acclaimed molecular biologist Dr. Nina Federoff. Dr. Van Eenennaam was also scheduled to participate in a news briefing on this topic at noon EST on Saturday, February 18, 2017 in Room 103 of the convention center. Thanks to improvements made in the dairy industry through traditional breeding, a glass of milk today is associated with just one third of the greenhouse gas emissions linked to producing a glass of milk in the 1940s, says Dr. Van Eenennaam, a UC Cooperative Extension biotechnology specialist in the UC Davis Department of Animal Science. That was accomplished as traditional selective breeding improved the productivity of dairy cows so much that the number of dairy cows in the United States dropped from a high of 25.6 million in 1944 to about 9 million today, even as the country experienced a 1.6-fold increase in total milk production, she says.

Capricor to Focus on Advancing Cardiac Cell and Exsosome-Based Therapeutic Candidates

On February 16, 2017, Capricor Therapeutics, Inc. (NASDAQ: CAPR), a clinical-stage biotechnology company developing first-in-class biological therapies for cardiac and other medical conditions, announced that it has elected to terminate its license agreement with the Mayo Clinic relating to natriuretic peptide receptor agonists, including Cenderitide. "Our decision to return these rights is a strategic move as we prioritize our efforts to advance our core cell and exosome-based therapeutic development programs," said Dr. Linda Marbán, Ph.D., President and Chief Executive Officer. "We enter 2017 with the anticipation of several key events to occur this year. These include our expected announcement early next quarter of top-line results of our randomized Phase I/II HOPE clinical trial of CAP-1002 (allogeneic cardiosphere-derived cells) in people with Duchenne muscular dystrophy (DMD)-associated heart disease, as well our expectation to clinically evaluate CAP-1002 for its ability to improve peripheral and respiratory muscle in DMD in a trial that is currently being planned. We are also committing increased attention to our exosomes program, and we expect to file an Investigation New Drug application for CAP-2003 (cardiosphere-derived cell exosomes) in the second half of this year," added Dr. Marbán. Capricor Therapeutics (formerly Nile Therapeutics, Inc.) entered into an Amended and Restated Technology License Agreement in 2013 around the time of the corporate merger. Since that time, Capricor has completed two small Phase II studies of Cenderitide, also known as CD-NP, in subjects with chronic, stable heart failure. Capricor Therapeutics, Inc.

Yeast Found in Babies’ Guts Increases Risk of Asthma

University of British Columbia (UBC) microbiologists have found a yeast in the gut of new babies in Ecuador that appears to be a strong predictor that they will develop asthma in childhood. The new research furthers our understanding of the role microscopic organisms play in our overall health. "Children with this type of yeast called Pichia were much more at risk of asthma," said Dr. Brett Finlay, a microbiologist at UBC. "This is the first time anyone has shown any kind of association between yeast and asthma." In previous research, Dr. Finlay and his colleagues identified four gut bacteria in Canadian children that, if present in the first 100 days of life, seem to prevent asthma. In a follow-up to this study, DR. Finlay and his colleagues repeated the experiment using fecal samples and health information from 100 children in a rural village in Ecuador. Canada and Ecuador both have high rates of asthma with about 10 per cent of the population suffering from the disease. The scientists found that while gut bacteria play a role in preventing asthma in Ecuador, it was the presence of a microscopic fungus or yeast known as Pichia that was more strongly linked to asthma. Instead of helping to prevent asthma, however, the presence of Pichia in those early days puts children at risk. Dr. Finlay also suggests there could be a link between the risk of asthma and the cleanliness of the environment for Ecuadorian children. As part of the study, the researchers noted whether children had access to clean water. "Those that had access to good, clean water had much higher asthma rates and we think it is because they were deprived of the beneficial microbes," said Dr. Finlay. "That was a surprise because we tend to think that clean is good, but we realize that we actually need some dirt in the world to help protect you." Now Dr.

Gene Sequences Reveal Secrets of Symbiosis

Advances in genomic research are helping scientists to reveal how corals and algae cooperate to combat environmental stresses. King Abdullah University of Science & Technology (KAUST) researchers have sequenced and compared the genomes of three strains of Symbiodinium, a member of the dinoflagellate algae family, to show their genomes have several features that promote a prosperous symbiotic relationship with corals. The article was published online on December 22, 2016 in Scienctific Reports. The open-access article is titled “Genomes of Dinoflagellate Symbionts Highlight Evolutionary Adaptations Conducive to a Symbiotic Lifestyle.” Dinoflagellates are among the most prolific organisms on the planet, forming the basis of the oceanic food chain, and their close symbiotic relationships with corals help maintain healthy reefs. However, because dinoflagellates have unusually large genomes, very few species have been sequenced, leaving the exact nature of their symbiosis with corals elusive. "We had access to two Symbiodinium genomes, S.minutum and S.kawagutii, and we decided to sequence a third, S. microadriaticum," said Assistant Professor of Marine Science Dr. Manuel Aranda at the University's Red Sea Research Center, who led the project with his Center colleague Associate Professor of Marine Science Dr. Christian Voolstra and colleagues from the University's Computational Bioscience Research Center and Environmental Epigenetics Program. "This allowed us to compare the three genomes for common and disparate features and functions and hopefully to show how the species evolved to become symbionts to specific corals."

February 18th

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."