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August 20th, 2018

Maple Leaf Extract May Prevent Wrinkles, According to Presentation at ACS Meeting in Boston

Maple trees are best known for their maple syrup and lovely fall foliage. But it turns out that the beauty of those leaves could be skin-deep -- and that's a good thing. Today, scientists report that an extract from the leaves may prevent wrinkles. The researchers are presenting their results at the 256th National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world's largest scientific society, is holding the meeting in Boston August 19-August 23, 2018. The ACS meeting features more than 10,000 presentations on a wide range of science topics. The maple leaf scientists had previously studied the chemistry and health benefits of sap and syrup obtained from sugar maple and red maple trees. Historical records suggested that other parts of the trees could also be useful, according to Navindra P. Seeram, PhD, the project's principal investigator. "Native Americans used leaves from red maple trees in their traditional system of medicine," he notes, "so why should we ignore the leaves?" Skin elasticity is maintained by proteins such as elastin. Wrinkles form when the enzyme elastase breaks down elastin in the skin as part of the aging process. "We wanted to see whether leaf extracts from red maple trees could block the activity of elastase," says Hang Ma, PhD, who is presenting the work at the ACS meeting and is a research associate in Dr. Seeram's lab. The researchers, who are at the University of Rhode Island, zeroed in on phenolic compounds in the leaves known as glucitol-core-containing gallotannins (GCGs) and examined each compound's ability to inhibit elastase activity in a test tube.

“Liquid Biopsy” (ctDNA) Predicts Lymphoma Therapy Success Within Days, Stanford-Led Study Finds

A blood test can predict which patients with a type of cancer called diffuse large B cell lymphoma are likely to respond positively to initial therapy and which are likely to need more aggressive treatment, according to a multicenter study led by researchers at the Stanford University School of Medicine. The study validates the clinical usefulness of tracking the rise and fall of circulating tumor DNA (ctDNA) in the blood of patients before and after therapy. It suggests that clinicians may soon be able to determine how a patient is responding to treatment within days or weeks of starting therapy rather than waiting until therapy is completed five to six months later. "Although conventional therapy can cure the majority of patients with even advanced B cell lymphomas, some don't respond to initial treatment," said Associate Professor of Medicine Ash Alizadeh, MD, PhD. "But we don't know which ones until several months have passed. Now, we can predict nonresponders within 21 days after the initiation of treatment by tracking the levels of ctDNA in a patient's blood. We can look earlier and make a reliable prediction about outcome." The study was published online on August 20, 2018 in the Journal of Clinical Oncology. The article is titled “Circulating Tumor DNA Measurements As Early Outcome Predictors in Diffuse Large B-Cell Lymphoma.” Dr. Alizadeh shares senior authorship with Associate Professor of Radiation Oncology Maximilian Diehn, MD, PhD. Instructor of Medicine David Kurtz, MD, PhD, and postdoctoral scholar Florian Scherer, MD, are the lead authors. Diffuse large B cell lymphoma, a blood cancer, is the most common type of non-Hodgkin lymphoma.

Hydrogel Technique for Delivering Muscle Stem Cells to Injured, Aging Muscle Tissue Is Successful in Model System; Technique May Ultimately Be Applicable to Duchenne Muscular Dystrophy

A car accident leaves an aging patient with severe muscle injuries that won’t heal. Treatment with muscle stem cells from a donor might restore damaged tissue, but doctors are unable to deliver them effectively. A new method may help change this. Researchers at the Georgia Institute of Technology (Georgia Tech) engineered a molecular matrix, a hydrogel, to deliver muscle stem cells called muscle satellite cells (MuSCs) directly to injured muscle tissue in patients whose muscles don’t regenerate well. In lab experiments on mice, the hydrogel successfully delivered MuSCs to injured, aged muscle tissue to boost the healing process while protecting the stem cells from harsh immune reactions. The method was also successful in mice with a muscle tissue deficiency that emulated Duchene muscular dystrophy, and if research progresses, the new hydrogel therapy could one day save the lives of people suffering from the disease. Simply injecting additional muscle satellite cells into damaged, inflamed tissue has proven inefficient, in part because the stem cells encounter an immune system that opposes them. “Any muscle injury is going to attract immune cells. Typically, this would help muscle stem cells repair damage. But in aged or dystrophic muscles, immune cells lead to the release a lot of toxic chemicals like cytokines and free radicals that kill the new stem cells,” said Dr. Young Jang, an Assistant Professor in Georgia Tech’s School of Biological Sciences and one of the study’s principal investigators. Only between 1 and 20 percent of injected MuSCs make it to damaged tissue, and those that do, arrive there weakened. Also, some tissue damage makes any injection unfeasible, thus the need for new delivery strategies. “Our new hydrogel protects the stem cells, which multiply and thrive inside the matrix.

Cellect’s Stem Cell Selection Technology Patent Receives Notice of Allowance in Korea

On August 20, 2018, it was announced that, in Korea, Cellect recently signed a collaboration agreement with Cell2in to improve stem cell selection and expansion. The agreement covers use of the ApoTainer™ device, as well as methods employing the device in stem cell selection for conditions including graft-versus-host disease (GvHD). On August 20, 2018 in Tel Aviv, Israel, Cellect Biotechnology Ltd., a developer of a novel stem cell production technology and headquartered in Israel, announced that it has received a Notice of Allowance from the Korean Intellectual Property Office for its patent titled, "Devices and Methods for Selecting Apoptosis-Signaling Resistant Cells, and Uses Thereof.” This patent, recently granted to Cellect in Europe, addresses the Company's ApoTainer™ device which is used in conjunction with its platform ApoGraft™ technology. "As we expand the number of stem cell industry collaborations for Cellect worldwide, our international patent assets and protections become increasingly important. In the past six weeks alone, we entered into collaborations with companies in Germany, Switzerland, and Korea. Working with industry partners to improve the safety and efficacy of stem cells and expanding regenerative medicine's wide scale-availability and affordability are cornerstones of Cellect's strategy. Our growing IP estate supports this purpose," stated Cellect CEO Dr. Shai Yarkoni. The patent addresses Cellect's devices and methods for specifically selecting desired stem cells from a heterogeneous cell population for use in a range of medical indications. Through negative selection, Cellect's technology identifies mature cells that can be harmful to the recipient and selectively eliminates those cells through apoptosis (cell death).

Advance in Research on Treatment for Retinitis Pigmentosa—Knockdown & Replacement of Rhodopsin Gene in Dog Model

The last year has seen milestones in the gene therapy field, with FDA approvals to treat cancer and an inherited blinding disorder. New findings from a team led by University of Pennsylvania vision scientists, who have in the past taken gene therapies into clinical trials, are proving successful, this time treating a form of retinitis pigmentosa, a disease that progressively robs people of their night and peripheral vision before blindness develops. The researchers, from Penn's School of Veterinary Medicine and Perelman School of Medicine, in collaboration with University of Florida scientists, developed a therapy that effectively eliminates the abnormal copy of rhodopsin, a light-sensing molecule, and then restores it with a healthy copy of the protein. This knockdown and replacement approach preserved the retina's light-sensing photoreceptor cells in affected dogs, which can develop a very similar disease to affected humans. What's more, the scientists accomplished this using a single viral vector (AAV) to co-deliver the genetic material needed to achieve both the knockdown and replacement. Though more than 150 different mutations in rhodopsin have been identified to cause retinitis pigmentosa, this approach is intended to work regardless of the mutation or the mechanism by which rod photoreceptor cells, those responsible for vision in dim light, die. That means that a large percentage of patients with rhodopsin autosomal dominant retinitis pigmentosa could benefit if the therapy is found to be safe and effective in people. "It's a one treatment fits all," says Dr. William A. Beltran, Professor of Ophthalmology and Director of the Division of Experimental Retinal Therapies at Penn Vet and co-lead author of the study, which was published online on August 20, 2018 in PNAS.

August 17th

Perinatal Hypoxia Associated with Long-Term Cerebellar Learning Deficits and Purkinje Cell Misfiring

Oxygen deprivation associated with preterm birth leaves telltale signs on the brains of newborns in the form of alterations to cerebellar white matter at the cellular and the physiological levels. Now, an experimental model of this chronic hypoxia reveals that those cellular alterations have behavioral consequences. Chronic sublethal hypoxia is associated with locomotor miscoordination and long-term cerebellar learning deficits in a clinically relevant model of neonatal brain injury, according to a study led by Children's National Health System researchers published online August 13, 2018 in Nature Communications. The open-access article is titled “Neonatal Brain Injury Causes Cerebellar Learning Deficits and Purkinje Cell Dysfunction.” Using high-tech optical and physiological methods that allow researchers to turn neurons on and off and an advanced behavioral tool, the research team finds that Purkinje cells fire significantly less often after injury due to perinatal hypoxia. However, an off-the-shelf medicine now used to treat epilepsy enables those specialized brain cells to regain their ability to fire, improving locomotor performance. Step out of the car onto the pavement, hop up to the level of the curb, stride to the entrance, and climb a flight of stairs. Or, play a round of tennis. The cerebellum coordinates such locomotor performance and muscle memory, guiding people of all ages as they adapt to a changing environment. "Most of us successfully coordinate our movements to navigate the three-dimensional spaces we encounter daily," says Vittorio Gallo, PhD, Children's Chief Research Officer and the study's senior author. "After children start walking, they also have to learn how to navigate the environment and the spaces around them." These essential tasks, Dr.

Genetic Differences in Trees’ Susceptibility to Mountain Pine Beetle

A University of Montana (UM) researcher has discovered that mountain pine beetles may avoid certain trees within a population they normally would kill due to genetics in the trees. UM Professor Dr. Diana Six made the discovery after studying mature whitebark and lodgepole trees that were the age and size that mountain pine beetle prefer, but had somehow escaped attack during a recent outbreak. After DNA screening, survivor trees were all found to contain a similar genetic makeup that was distinctly different from that of the general population that were mostly susceptible to the beetle. "Our findings suggest that survivorship is genetically based and, thus, heritable," Dr. Six said, "which is what gives us hope." In western North America, whitebark pine, a high elevation keystone species recommended for listing as an endangered species, and lodgepole pine, a widespread ecologically and economically important tree, have experienced extensive mortality in recent climate-driven outbreaks of the mountain pine beetle. "Our results suggest that surviving trees possess a wealth of information that can be used to inform our understanding of the genetic and phenotypic bases for resistance and to develop management approaches that support forest adaptation," Dr. Six said. The study was published July 23, 2018 in Frontiers in Plant Science. The open-access article is titled “Are Survivors Different? Genetic-Based Selection of Trees by Mountain Pine Beetle During a Climate Change-Driven Outbreak in a High-Elevation Pine Forest.”

[Press release] [Frontiers in Plant Science article]

August 17th

CRISPR Tool Reactivates Silenced FMR1 Gene of Fragile X Syndrome in Human Stem Cells

Using a gene editing tool, researchers successfully reactivated the FMR1 gene — which is silenced in fragile X syndrome patients — in human stem cells. This news was reported on August 16, 2018 in an article in Fragile X News Today written by Diogo Pinto. The open-access scientific article, “Targeted Reactivation of FMR1 Transcription In Fragile X Syndrome Embryonic Stem Cells,” was published online on August 15, 2018 in Frontiers in Molecular Neuroscience. Fragile X syndrome (FXS) is caused by a mutation in the FMR1 gene that results from the addition of three extra nucleotides — the building blocks of DNA — to its sequence. This is called a CGG repeat, which varies in number from 5 to 55 in healthy individuals. The more repeats, the higher the risk of developing the disease. This mutation results in the loss of the fragile X mental retardation protein (FMRP), the protein that is produced by the FMR1 gene. Treatments tested so far attempt to compensate for the loss of the FMRP protein and usually target only one of the protein’s functions. However, they have proven insufficient to treat the disease. Researchers believe one potential explanation for the lack of success in human clinical trials to date is that the different functions played by FMRP in nerve cells and other cell types may be difficult to correct with any treatment targeting only one dysregulated molecular pathway. In the newly reported therapeutic approach, researchers from the University of Michigan and the VA Ann Arbor Healthcare System used the CRISPR/Cas9 gene editing technology to target the CGG repeat that causes the mutation, and reactivates transcription of the silenced FMR1 gene. The CRISPR/Cas9 system is a genome editing tool that can edit parts of the genome by removing, adding, or altering sections of the DNA sequence.

Scientists ID Nearly 200 Interactions Between Tuberculosis Proteins and Human Proteins; These Human Proteins Represent Potential New Targets for TB Treatment and Prevention

Tuberculosis is one of the top ten causes of death worldwide. Nearly 2 million people die every year from this infectious disease, and an estimated 2 billion people are chronically infected. The only vaccine, developed almost 100 years ago, offers limited protection and patients are becoming increasingly resistant to available drugs. Despite this significant impact on humankind, very little is known about how tuberculosis develops and spreads in the body. A group of researchers from the Gladstone Institutes, UC San Francisco (UCSF), and UC Berkeley used a systematic approach to get an entirely new look at the way tuberculosis infects people. Their study, published in the august 16, 2018 issue of Molecular Cell, uncovered interactions between tuberculosis and human proteins that could provide new approaches to combat infection. The article is titled “An Mtb-Human Protein-Protein Interaction Map Identifies a Switch Between Host Anti-Viral and Anti-Bacterial Responses.” "With a better understanding of the mechanisms used by tuberculosis to disrupt our immune response, we could eventually optimize vaccine strategies, as well as explore therapies to supplement antibiotics," said Nevan J. Krogan, PhD, Senior Investigator at the Gladstone Institutes and Director of the Quantitative Biosciences Institute at UCSF. Tuberculosis is a complex disease, given that it's caused by a mycobacterium made up of 4,000 genes, as compared to viruses that generally have 10 or 15 genes. During infection, these genes produce approximately 100 proteins inside human cells. But, until now, scientists knew virtually nothing about what these proteins do in the body. Dr. Krogan, along with his colleague Jeffery S.

August 16th

Complex Wheat Genome (5X Size of Human Genome) Sequenced in Culmination of 13-Year Effort; DNA Sequence of World’s Most Cultivated Crop Should Contribute to Global Food Security

In the August 17, 2018 issue of Science, the International Wheat Genome Sequencing Consortium (IWGSC) published a detailed description of the genome of bread wheat, the world’s most widely cultivated crop. This work will pave the way for the production of wheat varieties better adapted to climate challenges, with higher yields, enhanced nutritional quality and improved sustainability. The research article – authored by more than 200 scientists from 73 research institutions in 20 countries – presents the reference genome of the bread wheat variety Chinese Spring. The article is titled “Shifting the Limits In Wheat Research and Breeding Using a Fully Annotated Reference Genome.” The DNA sequence ordered along the 21 wheat chromosomes is the highest-quality genome sequence produced to date for wheat. It is the result of 13 years of collaborative international research. A key crop for food security, wheat is the staple food of more than a third of the global human population and accounts for almost 20% of the total calories and protein consumed by humans worldwide, more than any other single food source. It also serves as an important source of vitamins and minerals. To meet future demands of a projected world population of 9.6 billion by 2050, wheat productivity needs to increase by 1.6 per cent each year. In order to preserve biodiversity, water, and nutrient resources, the majority of this increase has to be achieved via crop and trait improvement on land currently cultivated rather than committing new land to cultivation. With the reference genome sequence now completed, breeders have at their disposal new tools to address these challenges.