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Archive - Mar 9, 2019

Newly ID’d Pathway & Aging--NORAD (Non-Coding RNA Activated by DNA Damage) & PUMILIO Protein Play Key Roles in Maintenance of Genome Stability & Mitochondrial Function—Defects May Be Significant in Premature Aging Diseases Such As Progerias

Building upon their earlier discoveries, researchers at the University of Texas (UT) Southwestern have identified a new genetic pathway that prevents premature aging. Published online on February 8, 2019 in eLife, the study investigated the activity of the gene NORAD, which codes for a long noncoding RNA. The title of the article is “PUMILIO Hyperactivity Drives Premature Aging of Norad-Deficient Mice.” NORAD, which stands for “noncoding RNA activated by DNA damage,” is present in many mammals and helps maintain the appropriate number of chromosomes as cells divide. Many RNAs in the cell serve as the instructions, or code, for building proteins, whereas noncoding RNAs do not encode proteins. “There are many questions in the scientific community regarding the importance of noncoding RNAs in mammalian physiology and development,” said Dr. Joshua T. Mendell, Professor of Molecular Biology at UT Southwestern and senior author of the study. “Our cells produce thousands of these RNAs, but only a few have been connected to important functions in animals.” In 2015, the researchers reported their discovery of NORAD and demonstrated the importance of this noncoding RNA in maintaining the correct number of chromosomes in human cells. With their previous work limited to cells grown in the laboratory, the researchers next examined the role of NORAD in a living animal, in order to better understand the gene’s function in mammalian physiology. To accomplish this, Dr. Florian Kopp, a postdoctoral researcher in the Mendell lab and lead author of the eLife study, genetically engineered mice by deleting NORAD from the mouse genome. As has previously been found in human cells, the loss of NORAD caused chromosomal defects in mice. But there were also some unexpected changes to mitochondria, the energy powerhouses of the cell.

Exosomes Derived from PMSCs and Expressing Galectin 1 on Surface May Protect Neurons & Reduce Spinal Cord Injury, Offering Promising Prospect of Cell-Free Treatment, Spina Bifida Researchers at UC Davis Conclude

Researchers on the path to finding a cure for spina bifida have identified specific elements in stem cell secretions as key to protecting neurons and ultimately reducing the lower-limb paralysis associated with the birth defect. Those elements are exosomes (sub-cellular, membrane-bound vesicles that can transfer molecules from cell to cell) and a small carbohydrate-binding protein known as galectin 1. The research team will use the results to optimize the neuroprotective qualities of a stem cell treatment they have developed to improve the mobility issues associated with spina bifida. The new results were published online on February 12, 2019 in The FASEB Journal. The study was led by Aijun Wang (photo), PhD, Co-Director of the UC Davis Health Surgical Bioengineering Laboratory, and the article is titled “Neuroprotective Effect of Placenta-Derived Mesenchymal Stromal Cells: Role of Exosomes.” UC Davis Health fetal surgeon, and study co-author Diana Farmer, MD, Chair of the UC Davis Department of Surgery, first showed that prenatal surgery reduces neurological defects in children with spina bifida, which occurs when the spinal cord does not properly close before birth. Children with the condition experience a range of lifelong cognitive, urological, musculoskeletal and motor disabilities. Dr. Farmer, and Dr. Wang, her chief collaborator, later showed that prenatal surgery combined with human placenta-derived mesenchymal stromal cells (PMSCs) improved hind limb control in lab animals and dogs with spina bifida. Dr. Farmer is a Diana Farmer is a leader in research and surgical approaches to reduce the effects of spina bifida on children. “We wanted to know the specific mechanisms of action of the PMSC treatment that protect neurons,” Dr. Wang said.

Two Life-Saving Discoveries Help Four Generations of Women in One Family Deal with Familial Hypercholesterolemia; World-Leading Cholesterol Research at UT Southwestern Medical Center Led to Development of Game-Changing Statins, Then PCSK9 Inhibitors

Her great-grandmother volunteered in ground-breaking cholesterol research at the University of Texas (UT) Southwestern Medical Center. Now, 9-year-old Zoe Allen is benefiting from that decision. Four generations of women, who all have the same hereditary condition – familial hypercholesterolemia – form a story interwoven with the discovery of new treatments that have benefited millions of people. In 1987, Kathryn Geddie was a 33-year-old mother of two. At her annual physical, she told her doctor that her mother had extremely high cholesterol levels at a young age. After testing, Kathryn learned she had the same condition and began taking statins. “My mother is the reason that I was tested. My physician began treating me in 1987 because my cholesterol was in the upper 300s,” remembered Kathryn, now 64. Kathryn’s immediate concern drove her to have her then 11-year-old daughter, Shanon, tested. Despite her young age, Shanon’s cholesterol was soaring at 400 mg/dL. The normal range is less than 200. Little did the family know then that their shared struggle with high cholesterol would lead them on a road to reverse the disease – one paved by the generation that came before them. (Photo here shows Kathryn, Shannon, & Zoe--See additional, larger pics at end of this article). In the early 1980s, Kathryn’s mother, Estelle, took part in leading-edge research at UT Southwestern Medical Center where molecular genetics professors Drs. Michael Brown and Joseph Goldstein were seeking answers to how people develop high cholesterol. These scientists identified the basic mechanism of cholesterol metabolism, which led to their being awarded the 1985 Nobel Prize in Physiology or Medicine. Soon after this discovery, statins were developed to lower cholesterol and help prevent heart disease. Thousands of adult patients benefited. However, there were unknown risks for children.