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Archive - Oct 2016

October 31st

Plenary Address on Using 3D Organoid Culture to Model Human Brain Development and Disease Highlights Day 2 of World Congress of Psychiatric Genetics in Jerusalem

JERUSALEM, OCTOBER 31. Day 2 of the XXIV World Congress of Psychiatric Genetics opened with a plenary address to over 300 attendees by Juergen Knoblich, Ph.D., of the Institute of Molecular Biotechnology in Vienna, Austria. Dr. Knoblich’s presentation was titled “Modeling Human Brain Development and Disease in Stem-Cell-Derived 3D Organoid Culture.” Dr. Knoblich’s address was followed, later in the morning, by three concurrent scientific sessions: “The Science of the Psychiatric Genomics Consortium (Part 1),” “Progress in Psychiatric Genetics in China,” and “Clinical Genetic Testing in Psychiatry: Prospects and Challenges.” In his address, Dr. Knoblich first noted a key difference between mouse and primate brain development in that primate brains develop a much larger cerebral cortex and that this is driven by the cortical stem cells undergoing symmetric cell division for a much longer time before switching to asymmetric cell division. Consequently, cortical disease and development cannot be modeled in the mouse and this drove Dr. Knoblich to develop a stem-cell-derived 3D organoid model of a human brain. With this model, he was able to demonstrate neuronal movement from the ventral to the dorsal region. He also gave the example of modeling microcephaly in a human organoid model. The patient was found to have a mutation in the CDK5Rap2 gene and the corresponding gene in fruit flies was known to be involved with centrosomin function.

October 30th

World Congress of Psychiatric Genetics Opens in Jerusalem

JERUSALEM, OCTOBER 30. The XXIV World Congress of Psychiatric Genetics “Bridging the Gap Between Genes, Brain Function, and Psychiatry” opened today in Jerusalem. Morning and afternoon talks featured educational presentations and were followed, in the early evening, by the opening plenary address by Dr. David Goldstein, Ph.D., Director of the Institute for Genomic Medicine at the Columbia University Medical Center. Dr. Goldstein’s address was titled “Toward Precision Medicine in Neurodevelopmental Diseases.” Dr. Goldstein noted that much of the media tends to describe precision medicine as being able to provide a genetics-based diagnosis that will lead directly to a new treatment addressing the underlying genetic problem. So far, however, this is rarely the case, Dr. Goldstein said. More frequent are cases where a genetic diagnosis leads to a direction for new treatment or cases where the genetic diagnosis does not even establish a direction for a new treatment. Dr. Goldstein gave examples from his experience of all three patterns, and then suggested an approach (cultured neuronal networks) by which to move the latter two less definitive patterns to the first pattern. The first clinical example was that of Cara, an 18-month-old girl with progressive neurological symptoms that had baffled the clinicians who then requested that Dr. Goldstein undertake a sequencing analysis of the young girl and her parents to see if that might reveal any clues. That sequencing effort showed that Cara had compound heterozygous mutations in the gene SLC5A2, which was known to code for a transporter for vitamin B12 and this suggested the treatment of simply giving the girl appropriate doses of B12 which proved effective.

October 26th

Study of Juvenile Survival in Oahu Albatross Population

Understanding population dynamics is crucial for the conservation of long-lived species like albatrosses, but collecting data on albatrosses before they reach adulthood and begin to breed is challenging. A new study, published online on October 26, 2016 in The Condor: Ornithological Applications, provides the first direct estimates of the population size and annual survival of young birds in Oahu's Laysan Albatross population, giving important new insights into the demographics of these "prebreeders." The article is titled “Juvenile Survival, Recruitment, Population Size, and Effects Of Avian Pox Virus in Laysan Albatross (Phoebastria immutabilis) on Oahu, Hawaii, USA.” Husband-and-wife team Eric VanderWerf and Lindsay Young of Pacific Rim Conservation spent 14 years banding 477 Oahu albatrosses as chicks and monitoring what became of them. Contrary to the prevailing belief that young albatrosses remain at sea until they're ready to breed, VanderWerf and Young found that 2% of birds first returned to the colony as one-year-olds, 7% as two-year-olds, and 17% as three-year-olds. These early returners provided a rare window into the lives of young birds, allowing VanderWerf and Young to determine that prebreeders make up almost half of the Oahu population. Once they made it through their first year after fledging, the annual survival of these young birds was very high, estimated at about 97%.One threat to albatross populations is the mosquito-borne disease known as avian pox virus. "Although albatrosses and many other seabirds have strong immunity to avian pox virus, this disease has a negative long-term effect on their survival and chance of obtaining a mate," says VanderWerf.

October 25th

First Direct Evidence That Migratory Bat Hibernates

Perched among the branches and needles of California's redwood forests are nestled wayfaring hoary bats (Lasiurus cinereus). A migratory species capable of traveling hundreds of miles, hoary bats may wander throughout western North America before settling into California's north sleep. While it is not unusual for some species of bat to migrate or other species to hibernate, it is unusual to find a species of bat that does both. Hoary bats are one of North America's largest bats at 5 inches in length and also one of the continent's most distinguished with its frosted fur from which it takes its name. Researchers with the U.S. Forest Service's Pacific Southwest Research Station have documented the first recorded evidence of hoary bats going into a state of torpor, or hibernation. Published online on October 4, 2016 in Scientific Reports and just in time for National Bat Week, October 24-31, "First Direct Evidence of Long-Distance Seasonal Movements and Hibernation in a Migratory Bat" reports newly discovered behaviors in hoary bats. "It's commonly assumed that species that migrate do so to reach areas that allow them to continue feeding and remain somewhat active throughout the winter," said lead author Ted Weller, Ph.D., an ecologist with the Forest Service. "But our findings surprised even our own research team by showing that hoary bats spend much of the winter in hibernation." In September 2014, Dr. Weller and his colleagues tagged several bats within Humboldt Redwoods State Park with GPS tracking devices and another group of bats with a device that monitored light levels, body temperatures, and activity, which allowed them to understand how bats responded to varying weather conditions.

Results Suggest That Known Gene Codes for Key Enzyme in Process of Color Changes in Autumn Leaves

In plants, the pigment chlorophyll plays a central role in photosynthesis: the process of converting sunlight to energy. This process involves creating a flow of electrons by removing one from a molecule and transferring it to another. The first step happens when an electron is transferred from chlorophyll molecule to a compound called pheophytin a. Autumn leaf colors occur when chlorophyll degrades as a normal part of leaf aging or "senescence," playing an important role in nitrogen recycling. The process of chlorophyll degradation is triggered when an enzyme extracts magnesium (Mg) from chlorophyll. Researchers have named the enzyme Mg-dechelatase, but have never been able to detect its actual presence in experiments. Yousuke Shimoda, Hisashi Ito, and Ayumi Tanaka at Hokkaido University in Japan have demonstrated that a gene with known involvement in chlorophyll degradation, called Stay-Green (SGR), codes for Mg-dechelatase. Stay-Green mutants allow leaves to retain greenness during senescence. This gene was among several that led Gregor Mendel to establish the basic laws of genetics in the 19th century while studying the characteristics of peas over several generations. However, it has long been unknown what the gene actually encodes. The Hokkaido team transiently induced SGR in fully green leaves of a small flowering plant called thale cress. They found this resulted in a reduction of chlorophyll levels. They also incubated chlorophyll in a test tube with SGR, which resulted in its conversion to pheophytin a. Chlorophyll can only be converted to pheophytin a by extracting Mg from it. The experiments strongly suggest that Mg-dechelatase is involved in chlorophyll degradation via SGR. The new results were published online on September 7, 2016 in The Plant Cell.

First-in-Humans Study Using EVs, Including Exosomes, Slated for Crohn’s Disease Treatment in 2017

According to an October 20, 2016 announcement, Esperite’s business unit The Cell Factory, in collaboration with the Women’s and Children’s Health Department of the University of Padua and the Padua University Hospital (Italy), is developing therapies for inflammatory bowel disease (IBD) using extracellular vesicles (EVs). The first target is Crohn’s disease perianal fistulas in adults. A first-in-man study using EVs, including exosomes, for treatment of Crohn’s disease perianal fistula will start in 2017. Inflammatory bowel disease (IBD) encompasses a spectrum of diseases affecting gastrointestinal tract. The most common are Crohn’s disease and ulcerative colitis. IBD is a chronic and often recurring inflammation of the intestines with unknown cause and limited treatment options. In the most severe cases of Crohn’s disease, the patients suffer from perianal fistulas that significantly affect normal activity and may lead to complications such as an increased risk of cancer and life-threating systemic inflammation. In Europe, the current treatment of Crohn’s disease is focused on anti-TNF-alpha therapy whereas anti-integrin biologics are an alternative available in the U.S. Unfortunately, perianal fistulas often do not respond to these systemic treatments. Several clinical trials are ongoing to target perianal fistulas using allogenic mesenchymal stem cells (MSCs) with very positive results. The approach at Esperite is focused on using extracellular vesicles (including exosomes) derived from mesenchymal stem cells (MSCs) for the first time in the treatment of inflammation responsible for Crohn’s disease perianal fistulas. Esperite has acquired the full rights of a broad patent family enabling MSC-derived EVs to be used in treatment of all autoimmune, chronic, and acute inflammatory diseases.

October 24th

Small RNA Linked to Pregnancy Complication of Preeclampsia

A family of small RNA molecules affects the development of cells that give rise to the placenta – an organ that transfers oxygen and nutrients from mother to fetus – in ways that could contribute to a serious pregnancy complication, UT Southwestern Medical Center researchers report. The findings, published online on October 24, 2016 in PNAS, suggest that microRNA-515-5p (miRNA-515-5p) might someday be the basis of a blood test to identify women at risk for the condition called preeclampsia, or lead to a target for treatment, said Dr. Carole Mendelson, Professor of Biochemistry, and Obstetrics and Gynecology at the University of Texas (UT) Southwestern Medical Center. The article is titled “Primate-Specific miR-515 Family Members Inhibit Key Genes in Human Trophoblast Differentiation and Are Upregulated in Preeclampsia.” This is one of the first studies to identify a specific function for any member of this large, multimember microRNA family, Dr. Mendelson said. Located on human chromosome 19, miRNA-515-5p is found only in primates and is primarily expressed in the placenta. During the third trimester of pregnancy, preeclampsia can come on suddenly and affect virtually every part of the body with symptoms that include dangerously high blood pressure, protein in the urine and, in severe cases, seizures. Preeclampsia is considered a significant contributor to premature births as well as to maternal and neonatal illness and death. The National Institutes of Health estimates preeclampsia affects 5 to 10 percent of pregnant women worldwide and 3 to 5 percent in the United States. According to the World Health Organization, about 40 to 60 percent of maternal deaths in developing countries are due to this condition.

Nail-Biting, Lou Gehrig’s Disease, and Late-Breaking Abstract Presentations on TOP-Med, Type 2 Diabetes, and Exome Sequencing of Newborns Among Highlights of Final Day of ASHG Annual Meeting in Vancouver

VANCOUVER, OCTOBER 23. Presentations on the genetics of nail-biting, the identification of genetic modifiers of age-of-onset of ALS (Lou Gehrig’s disease), and three late-breaking abstracts—one on the TOPMed (Trans-Omics for Precision Medicine) project, another on the epigenetics of type 2 diabetes, and the final presentation on work to evaluate the potential of exome sequencing for newborn screening were highlights of the final day of the annual meeting of the American Society of Human Genetics (ASHG) in Vancouver, Canada. Chao Tian (photo) of 23andMe presented her group’s GWAS studies that showed 24 significant genome associations with nail-biting. Interesting connections between nailbiting and depression, anxiety, and restless legs syndrome were noted. Hyerim Kim presented her group’s work on the identification of genetic modifiers of the age-of onset of ALS associated with the expanded GGGGCC repeats. Because of the difficulty in identifying truly ALS-associated rare varients, Ms. Kim did whole-genome sequencing and functional genomics in a fly model of ALS. The first of the three late-breaking abstract presentations focused on the National Heart, Blood, and Lung Institute’s (NHBLI’S) TOPMed study ( intended to accelerate advances, particularly in the areas of lung disease, cardiovascular disease, and blood disorders. The next presentation was on type 2 diabetes (TD2) and the speaker noted that more than 100 loci have been associated with diabetes and related disorders and that the majority of these loci are located in non-coding regions, particularly in enhancer regions—thus indicating problems in expression rather than function.

October 21st

Prestigious Prizes Awarded on Day 4 of ASHG Annual Convention in Vancouver

VANCOUVER, OCTOBER 21. The 2016 Gruber Genetics Prize was awarded today to molecular biologists Michael Grunstein, Ph.D., of the University of California Los Angeles (UCLA), and C. David Allis, Ph.D., of The Rockefeller University at the American Society of Human Genetics (ASHG) annual meeting in Vancouver, Canada. These two renowned scientists received this prestigious award for their groundbreaking work in identifying the critical role of histones and histone modifications in regulating gene activity. In addition, the ASG’s Arno Motulsky-Barton Childs Award for Excellence in Human Genetics Education was presented to David Valle (photo), M.D., and the Society’s inaugural Mentorship Award was presented to Elaine Zackai, M.D. Gruber prize winners Dr. Grunstein and Dr. Allis transformed the field of molecular biology and were instrumental in launching the modern study of histones in epigenetics, with broad implications for human health and disease. “These two remarkable scientists showed us that genetic coding is not determined solely by our inherited DNA, but also by a direct interaction between that DNA and histones, the proteins in cell nuclei around which DNA is tightly bound,” says Huda Zoghbi, M.D., Investigator, Howard Hughes Medical Institute at Baylor College of Medicine and chair of the Selection Advisory Board to the Gruber Genetics Prize. “Not only has this work profoundly changed our understanding of gene regulation, but it has also greatly advanced our knowledge of medical conditions as varied as birth defects, heart disease, and cancer.” For many years, histones were considered nothing more than the material that “packages” DNA into structures called nucleosomes, which are the building blocks of the chromatin complex that form chromosomes within the nucleus of eukaryotic cells. In the late 1980s, Dr.

October 20th

Ancient Human History More Complex Than Previously Thought; Drosophila Study Suggests Dietary Treatment Approach to an Extremely Rare Human Genetic Disease--Day 3 at ASHG Annual Meeting in Vancouver

VANCOUVER, OCTOBER 20. Exciting work on a Drosophila model of a rare human genetic disease and a provocative study showing that ancient human history is much more complex than previously thought were among many highlights of the third day of the American Society of Human Genetics (ASHG) annual meeting in Vancouver, Canada. Researchers studying Drosophila fruit flies have found that, in flies, providing a common dietary supplement prevents death caused by Pngl deficiency, the fly analog of the human genetic disorder N-Glycanase 1 (NGLY1) deficiency. NGLY1 deficiency, a rare, autosomal recessive disease, was first defined just four years ago and has been diagnosed in about 60 individuals worldwide, explained presenter Clement Y. Chow (photo), Ph.D., Assistant Professor in the Department of Human Genetics at the University of Utah and lead author on the study. People with this disease experience developmental delays, difficulty with movement, problems with liver function, and alacrima, the inability to produce tears. Symptoms are severe, starting from birth, and patients tend to live for less than ten years. The disease is caused by a lack of the enzyme NGLY1, which plays an important role in degrading misfolded proteins in the cell. Researchers believe that without NGLY1, these proteins accumulate in the cell's cytoplasm, remaining bound to, and depleting the cell's supply of, GlcNAc, a sugar available widely as the dietary supplement N-acetylglucosamine. NGLY1 is remarkably conserved across species, and the Drosophila analog Pngl is thought to play a similar, equally critical role in flies. In a cohort of flies engineered to lack a functional copy of Pngl, just 18 percent survive to adulthood. “Because GlcNAc is non-toxic and so widely available, we thought we’d try providing flies with it as a supplement to restore the cell's supply," Dr. Chow said.