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Archive - 2017

November 10th

Former NFL Football Players Twice As Likely to Have Enlarged Aortas; Health Risk Currently Unknown

Former NFL players were more likely to have enlarged aortas, but further study is needed to determine whether that puts them at greater risk for life-threatening aneurysms, researchers found. The former National Football League players were twice as likely to have enlarged aortas as those in a control group, even after adjusting for their typically larger size and other factors, said researchers with the Dallas Heart Study at UT Southwestern Medical Center, from which the control group was drawn. “Whether that translates to the same risk for these former elite athletes as a dilated, or enlarged, aorta does for the general population is unclear,” said cardiologist Dr. Parag Joshi, Assistant Professor of Internal Medicine and one of the study’s authors. “Is this a normal adaptation from having trained at the elite level throughout their youth, or is this a bad adaptation that puts them more at risk for problems?” Former linemen – players who tend to be larger and engage in more strength training than non-linemen – were more likely to cross the threshold into the enlarged aorta range, suggesting that increased aortic diameter is an adaptation to the demands placed on a player’s heart during his career, said co-author and fellow cardiologist Dr. James de Lemos, Professor of Internal Medicine and Medical Director for the Dallas Heart Study. Nearly 30 percent of the former NFL players studied had enlarged aortas compared with less than 9 percent in the comparison group from the Dallas Heart Study, a one-of-a-kind population-based study to identify new genetic, protein, and imaging biomarkers that can detect cardiovascular disease at its earliest stages, when prevention is most effective.

November 9th

Transplant of Skin Derived from Genetically Modified Stem Cells Saves Life of Child with Life-Threatening Congenital Skin Disease (Epidermolysis Bullosa); 80% of Body Surface Transplanted in World-First Success

A medical team at the Ruhr-Universität Bochum’s burn unit (Germany) and the Center for Regenerative Medicine at the University of Modena (Italy) is the first ever to successfully treat a child suffering from extensive skin damage using transplants derived from genetically modified stem cells. The boy is a so-called butterfly child: he suffers from epidermolysis bullosa, a genetic skin disease that had destroyed approximately 80 percent of his epidermis. After all established therapies had failed, the medical team from Bochum decided to try an experimental approach: the doctors transplanted skin derived from genetically modified stem cells onto the wound surfaces. Thanks to the successful therapy, the boy is now – two years after the treatment – able to participate in his family’s life and social life. The scientists published their report online on November 8, 2017 in Nature. The article is titled “Regeneration of the Entire Human Epidermis by Transgenic Stem Cells.” Epidermolysis bullosa is the scientific name of a congenital skin disease that is currently considered to be incurable. Its underlying mechanism is a defect in protein-forming genes that are essential for skin regeneration. Even minor stress can result in blisters, wounds, and skin loss with scar formation. Depending on disease severity, internal organs may likewise be affected, leading to critical dysfunctions. The disease significantly reduces the patients’ quality of life; often it is also life-threatening, as in the case of Hassan, the seven-year-old: by the time he was admitted to the pediatric intensive care unit at Katholisches Klinikum Bochum in June 2015, 60 percent of his epidermis had been lost.

November 8th

Sheep Can Recognize Human Faces from Two-Dimensional Images

Sheep can be trained to recognize human faces from photographic portraits - and can even identify the picture of their handler without prior training - according to new research from scientists at the University of Cambridge (UK). The study, published online on November 8, 2017 in Royal Society: Open Science, is part a series of tests given to the sheep to monitor their cognitive abilities. The open-access article is titled “Sheep Recognize Familiar and Unfamiliar Human Faces from Two-Dimensional Images.” Because of the relatively large size of their brains and their longevity, sheep are a good animal model for studying neurodegenerative disorders such as Huntington's disease. The ability to recognize faces is one of the most important human social skills. We recognize familiar faces easily, and can identify unfamiliar faces from repeatedly presented images. As with some other animals such as dogs and monkeys, sheep are social animals that can recognize other sheep as well as familiar humans. Little is known, however, about their overall ability to process faces. Researchers from the University of Cambridge's Department of Physiology, Development, and Neuroscience trained eight sheep to recognize the faces of four celebrities from photographic portraits displayed on computer screens. The celebrities were Fiona Bruce, Jake Gyllenhaal, Barack Obama, and Emma Watson. Training involved the sheep making decisions as they moved around a specially-designed pen. At one end of the pen, they would see two photographs displayed on two computer screens and would receive a reward of food for choosing the photograph of the celebrity (by breaking an infrared beam near the screen); if they chose the wrong photograph, a buzzer would sound and they would receive no reward. Over time, they learn to associate a reward with the celebrity's photograph.

November 4th

Three-Step, Pre-Targeted Radioimmunotherapy Approach to Treating Colorectal Cancer Leads to Complete Cure in Mouse Model

Researchers at Memorial Sloan Kettering Cancer Center in New York City and Massachusetts Institute of Technology in Boston have developed a new, three-step system that uses nuclear medicine to target and eliminate colorectal cancer. In this study in a mouse model, researchers achieved a 100-percent cure rate--without any treatment-related toxic effects. The study is reported in the November 2017 featured article (image) in The Journal of Nuclear Medicine. The article is titled “Curative Multicycle Radioimmunotherapy Monitored by Quantitative SPECT/CT-Based Theranostics, Using Bispecific Antibody Pretargeting Strategy In Colorectal Cancer." Until now, radioimmunotherapy (targeted therapy) of solid tumors using antibody-targeted radionuclides has had limited therapeutic success. "This research is novel because of the benchmarks reached by the treatment regimen, in terms of curative tumor doses, with non-toxic secondary radiation to the body's normal tissues," explains Steven M. Larson, MD, and Sarah Cheal, PhD, both of Memorial Sloan Kettering Cancer Center. "The success in murine tumor models comes from the unique quality of the reagents developed by our group, and the reduction to practice methodology, including a theranostic approach that can be readily transferred, we believe, to patients." Theranostics, a term derived from therapy and diagnostics, is the use of a single agent to both diagnose and treat disease. The theranostic agent first finds the cancer cells, then destroys them, leaving healthy cells unharmed--minimizing side effects and improving quality of life for patients.

Tolvaptan Slows Progression of Autosomal Dominant Polycystic Disease (ADPKD) in Later-stage Disease in Phase 3 Trial; Treatment May Delay Need for Dialysis or Kidney Transplant

A phase 3 trial studying the effects of the vasopressin V2-receptor antagonist tolvaptan has found that the drug slowed the rate of decline in kidney function in patients with later stages of the most common form of polycystic kidney disease, a condition with no cure. The results were published online today (November 4, 2017) in the New England Journal of Medicine. The article is titled “Tolvaptan in Later-Stage Autosomal Dominant Polycystic Kidney Disease.” Autosomal dominant polycystic kidney disease (ADPKD) is an inherited condition that affects 1 in every 500 to 1,000 individuals in the U.S. This disease is found in all races and sexes. ADPDK, which is the fourth most common cause of end-stage kidney disease, ultimately requires dialysis or kidney transplant in many cases. The disease causes a slow but relentless growth of cysts that damage the kidneys. In addition to negatively affecting quality of life, the condition also causes hypertension and painful complications. The cysts, which can damage kidneys with their size, can also develop in other organs, especially the liver. Approximately half of individuals with ADPKD will eventually require dialysis or kidney transplant by age 60. The results of the trial demonstrated tolvaptan's ability to intervene in a way that slows kidney function decline in this population. Vasopressin promotes kidney-cyst cell proliferation and fluid secretion by means of up-regulation of adenosine-3′,5′-cyclic monophosphate (cAMP). The suppression of vasopressin production, release, or action by means of hydration, V2-receptor blockade, or genetic mutation has previously been shown to reduce cyst burden, protect kidney function, and prolong survival in rodent models.

November 3rd

Potential New Treatment for Fragile X Targets One Gene to Affect Many

In Fragile X Syndrome--the leading genetic form of intellectual disability and autism--the effects of a single defective gene ripple through a series of chemical pathways, altering signals between brain cells. It's a complex condition, but new research from Rockefeller University finds that inhibiting a regulatory protein alters the intricate signaling chemistry that is responsible for many of the disease's symptoms in animal models. The work, published in the Septmber 7, 2017 issue of Cell, offers insight into how redundant mechanisms control the amount of protein in a cell and provides a path to possible therapeutics for the autism spectrum disorders. The article is titled “Excess Translation of Epigenetic Regulators Contributes to Fragile X Syndrome and Is Alleviated by Brd4 Inhibition.” The work centers on a group of proteins--known as chromatin remodeling proteins--that control gene expression. Chromatin remodelers work by adding chemical tags to DNA, regulating the cellular machinery that transcribes genes into messages. "Drugs that target chromatin remodelers are already in clinical trials to treat cancers like leukemia," says study author Dr. Erica Korb, a postdoctoral researcher at Rockefeller. "It is an attractive approach because a single inhibitor allows you to target a whole network of genes at once." The new research suggests that chromatin remodeling proteins may similarly play a key role in Fragile X Syndrome. By targeting chromatin remodelers in animals, the scientists were able to successfully alleviate symptoms of the disease. Researchers have known for some time that Fragile X Syndrome is caused by defects in a single gene, known as FMRP, but exactly how FMRP affects neural function has remained a mystery. A break came in 2011, when Rockefeller's Dr. Robert B.

October 31st

Pumpkin Genomes Sequenced, Revealing Uncommon Evolutionary History

For some, pumpkins conjure carved Halloween decorations, but for many people around the world, these gourds provide nutrition. Scientists at Boyce Thompson Institute (BTI) in New York and the National Engineering Research Center for Vegetables in Beijing have sequenced the genomes of two important pumpkin species, Cucurbita maxima and Cucurbita moschata. The finished genomes appear in the October 9, 2017 issue of Molecular Plant, which highlights the work on its cover. The open-access article is titled “Karyotype Stability and Unbiased Fractionation in the Paleo-Allotetraploid Cucurbita Genomes.” "Pumpkins are used as a staple food in many developing countries and are cultivated all over the world for their culinary and ornamental uses," said Dt. Zhangjun Fei, Associate Professor at BTI, Cornell Adjunct Associate Professor of Plant Pathology and a senior author of the paper. Over two-thirds of the world's pumpkins, squash, and gourds are produced in Asia alone. The researchers sequenced the two different pumpkin species to better understand their contrasting desirable traits: Cucurbita moschata is known for its resistance to disease and other stresses, such as extreme temperatures, while C. maxima is better known for its fruit quality and nutrition. Additionally, the hybrid of these two species, called “Shintosa” has even greater stress tolerance than C. moschata, and is often used as a rootstock for other cucurbit crops, such as watermelon, cucumber, and melon. Growers will cut the pumpkin seedling from its roots, and fuse the stems of other cucurbits onto it, giving them strong, resistant roots to grow from. Once deciphered, the genome sequences are an important resource for further scientific research and breeding of Cucurbita crops.

Interest in Bipolar Disorder Drug Lithium Exposes Possible Link with Splicing Factors and May Lead to Better Understanding of Leukemia Progression

A research project that began 20 years ago with an interest in how lithium treats mood disorders has yielded insights into the progression of blood cancers such as leukemia. The open-access article, which centers on a protein called GSK-3, was published online on September 15, 2017, and will be published in the November 3, 2017 issue of the Journal of Biological Chemistry. The article is titled “Phosphoproteomics Reveals That Glycogen Synthase Kinase-3 Phosphorylates Multiple Splicing Factors and Is Associated with Alternative Splicing.” Lithium is considered a highly effective treatment for bipolar disorder and other mood disorders, but it still works in only a fraction of patients and has a number of side effects. Furthermore, its mechanism of action is poorly understood, hampering efforts to improve on it. In 1996, Dr. Peter Klein of the University of Pennsylvania discovered that one of lithium's biological activities was inhibiting GSK-3, an enzyme that modifies other proteins by attaching phosphate molecules, a process called phosphorylation. Lithium's effect on GSK-3 affected the development of animal cells, but it is still unknown what connection, if any, this has to psychiatric disease. Since then, Dr. Klein, now a professor of medicine at the University of Pennsylvania, has been investigating many different aspects of GSK-3 activity. "In this paper, we were trying to find out what proteins in the cell are affected by GSK-3 inhibition," Dr. Klein said. "We compared cells with GSK-3 to cells completely lacking GSK-3 to ask how other proteins changed." "Mood disorders are so multifaceted in terms of the pathways and pathologies involved; it's really difficult to pin down a specific pathway," said Dr. Mansi Shinde, a former graduate student in Dr. Klein's research group who led the new study.

Scientists Unveil Sequence of Water Buffalo Genome

An international team of researchers led by the University of Adelaide in Australia has published the full genome of the water buffalo - opening the way for improved breeding and conservation of this economically important animal. The consortium of partners in Australia, Italy, China, Brazil, and the USA, with additional contributors in other countries, say they have now created the tools needed to apply modern molecular breeding systems to water buffalo. "Water buffaloes were domesticated about 5,000 years ago, and since then have been of economic importance for milk, meat, and as a work animal around the world," says consortium leader Professor John Williams, Director of the University of Adelaide's Davies Research Centre at the Roseworthy campus. "They are particularly important in developing countries and, in specialized markets, they provide milk for products such as mozzarella cheese in Italy. The water buffalo is a key agricultural animal because it is able to adapt to diverse environments, and is particularly tolerant of disease. "In Australia, they were brought to Northern Territory in the early 19th century and today there are milking herds of buffalo in Northern Territory and in South Australia." There are two subspecies of water buffalo. The researchers sequenced the genome of the River buffalo, which have been selected for milk production through organized breeding programs in Italy, India, the Philippines, and Brazil. Professor Williams says such advances in genomics have revolutionized dairy cattle breeding and now the same molecular tools will be available for water buffalo breeding. This project is another great example of the University of Adelaide's depth and expertise in research areas related to food innovation.

October 29th

Exosome-Associated MicroRNAs May Be Powerful Biomarkers for Multiple Sclerosis, New Study Shows

A breakthrough study led by the University of Sydney's Brain and Mind Centre and Royal Prince Alfred Hospital has revealed unique molecules in the blood of people with multiple sclerosis (MS) that could become definitive diagnostic biomarkers of the world's most common neurologic disability in young adults. Published online today (October 30, 2017) in Scientific Reports, the discovery identifies tiny “dysregulated” micro-RNA molecules that correctly diagnose MS and discriminate between patients at different disease stages - all in a simple blood test. The open-access article is titled “Exosomal MicroRNA Signatures in Multiple Sclerosis Reflect Disease Status.” Currently, there is no definitive test for MS. Diagnosis and disease monitoring rely on several parameters, including clinical examination, MRI, cerebrospinal fluid assessment, and electrophysiology. MS is a chronic disease, so current diagnostic and monitoring tests are costly and still have limited utility to discriminate between different stages of the disease. In addition to identifying biomarkers that distinguish healthy people from those with MS, the researchers identified nine unique micro-RNA molecules that differentiate between two MS sub-types: relapsing-remitting MS (RRMS) and progressive MS. Relapsing-remitting MS (RRMS) affects 70 percent of MS patients and often evolves into a secondary progressive form of MS. 10-15 percent of people with MS are diagnosed with a progressive form of the disease from the outset known as primary progressive MS. The team also validated eight out of nine micro-RNA molecules in an independent group of progressive MS cases, confirming the reproducibility of the findings.