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Archive - Jan 6, 2017

Elevated Levels of Tau Protein Associated with Longer Recovery from Concussion

Elevated levels of the brain protein tau following a sport-related concussion are associated with a longer recovery period and delayed return to play for athletes, according to a study published online on January 6, 2017 in Neurology®, the medical journal of the American Academy of Neurology. The findings suggest that tau, which can be measured in the blood, may serve as a marker to help physicians determine an athlete's readiness to return to the game. The article is titled “Acute Plasma Tau Relates to Prolonged Return to Play After Concussion.” Despite the 3.8 million sports-related concussions that occur annually in the United States, there are no objective tools to confirm when an athlete is ready to resume play. Returning to play too early, before the brain has healed, increases an athlete's risk of long-term physical and cognitive problems, especially if he or she sustains another concussion. Currently, physicians and trainers must make return-to-play decisions based on an athlete's subjective, self-reported symptoms and their performance on standardized tests of memory and attention. A team led by Jessica Gill, R.N., Ph.D. of the National Institute of Nursing Research at the National Institutes of Health and Jeffrey Bazarian, M.D., M.P.H. of the University of Rochester Medical Center evaluated changes in tau in 46 Division I and III college athletes who experienced a concussion. Tau, which plays a role in the development of chronic traumatic encephalopathy or CTE, frontotemporal dementia, and Alzheimer's disease was measured in preseason blood samples and again within 6 hours following concussion using an ultra-sensitive technology that allows researchers to detect single protein molecules.

Research Reveals How Bacteria Resist “Last-Resort” Antibiotic

An international research team, led by the University of Bristo (UK), has provided the first clues to understand how the mcr-1 gene protects bacteria from colistin - a 'last resort' antibiotic used to treat life-threatening bacterial infections that do not respond to other treatment options. Last year, members of the team, led by Dr. Jim Spencer from the School of Cellular and Molecular Medicine, in collaboration with colleagues from Oxford, Cardiff, Diamond Light Source, Thailand, and China, identified mcr-1 as the first colistin-resistance gene that could be passed between bacteria, enabling resistance to spread rapidly within a bacterial population. Since then, the mcr-1 gene has been detected in common bacteria, such as E. coli, in China, the United States, and across Europe, first in farm animals and recently - worryingly - in human patients. The spread of mcr-1 has been linked to agricultural use of colistin, indicating that transmission between animals and humans may take place. In response to these findings the Chinese government has now banned use of colistin in animal feed. Colistin acts by binding to, and disrupting, the outer surface of bacteria. Bacteria carrying the mcr-1 gene make a protein that modifies the bacterial surface to reduce colistin binding, making the organism resistant. In its work, the team used X-rays produced at Diamond's crystallography beamlines to generate detailed pictures of the portion of this protein responsible for this modification, and with this information identified key features that are necessary for it to function. They also constructed computer models of the chemical reaction that leads to resistance.

New Treatment for Rare Form of Encephalitis

“Anti-NMDA-receptor encephalitis” is an inflammatory disease that affects the central nervous system. It is a rare autoimmune disease that results in the body producing antibodies against the NMDA receptor (image), a protein that plays an important role in signal transduction in the brain. Using a new treatment regimen, researchers from Charité-Universitätsmedizin Berlin and the German Center for Neurodegenerative Diseases (DZNE) have recorded significant progress in treating the disease, including in patients who did not previously respond to treatment. Results from this study were published online on December 21, 2016 in the journal Neurology. The article is titled “Bortezomib for Treatment of Therapy-Refractory Anti-NMDA Receptor Encephalitis.” Anti-NMDA-receptor encephalitis is a serious autoimmune disease. It is characterized by an inflammation of the brain, which can result in neurological and psychiatric symptoms, including psychoses, epileptic seizures, and movement disorders. Standard treatments currently available are often either inadequate or ineffective in patients with severe forms of the disease. This treatment resistance may be caused by certain anti-NMDA-receptor antibody-producing plasma cells that remain inaccessible to current immunotherapies. In a study led by Dr. Franziska Scheibe and Professor Dr. Andreas Meisel from the Department of Neurology and the NeuroCure Cluster of Excellence, Charité-based researchers recorded outcomes obtained using a new treatment regimen. In addition to standard treatment, patients received bortezomib, a drug known as a proteasome inhibitor that has proven successful in treating patients with plasmacytoma, a specific type of blood cancer.

Comprehensive Interactome Map of Human Receptor Tyrosine Kinases and Phosphatases Is Released; Paves Way for Future Cancer Research and Drug Discovery

In 2011, Igor Stagljar, Ph.D., a professor in the University of Toronto's Donnelly Centre, came across a study that genetically linked two genes in the cell to a hard-to-treat (triple negative) breast cancer. It was not clear how the proteins encoded by these genes worked, but Dr. Stagljar had a unique way to find out. One of the proteins, called epidermal growth factor receptor (EGFR), belonged to a group called receptor tyrosine kinases (RTKs), which tell the cell to grow and divide in response to signals from the cell's environment. The other one (PTPN12) was from the protein tyrosine phosphatase (PTP) class, which mainly work by shutting the RTKs down. However, the EGFR is wedged within the cell's outer envelope, or membrane, making it difficult to study by traditional methods. But with the help of MYTH and MaMTH, technologies developed in Stagljar's lab, Dr. Zhong Yao, a senior research associate in the lab, was able to show that the two proteins came into direct contact with each other. This led further support to the thinking that some breast cancers progress when the link between this particular RTK and PTP is broken, unleashing unchecked RTK signalling and, consequently, cell proliferation. But Dr. Yao did not stop there. The high-throughput power of MYTH and MaMTH allowed him to investigate interactions between almost all human RTKs and PTPs. The resulting map charts more than 300 RTK-PTP interactions, most of which were unknown. The study was published online in the journal Molecular Cell on January 5, 2017. The article is titled “A Global Analysis of the Receptor Tyrosine Kinase-Protein Phosphatase Interactome.” "We tested interactions between almost all 58 RTKs and 144 PTPs that exist in human cells. Our map reveals new and surprising ways in which these proteins work together.

Researchers Find Key Genetic Driver for Rare Type of Triple-Negative Breast Cancer

For more than a decade, Celina Kleer, M.D., has been studying how a poorly understood protein called CCN6 affects breast cancer. To learn more about its role in breast cancer development, Dr. Kleer's lab designed a special mouse model - which led to something unexpected. The scientists deleted CCN6 from the mammary gland in the mice. This type of model allows researchers to study effects specific to the loss of the protein. As Dr.Kleer and her team checked in at different ages, they found delayed development and mammary glands that did not develop properly. "After a year, the mice started to form mammary gland tumors. These tumors looked identical to human metaplastic breast cancer, with the same characteristics. That was very exciting," says Dr. Kleer, Harold A. Oberman Collegiate Professor of Pathology and Director of the Breast Pathology Program at the University of Michigan Comprehensive Cancer Center. Metaplastic breast cancer is a very rare and aggressive subtype of triple-negative breast cancer - a type considered rare and aggressive of its own. Up to 20 percent of all breast cancers are triple-negative. Only 1 percent are metaplastic. "Metaplastic breast cancers are challenging to diagnose and treat. In part, the difficulties stem from the lack of mouse models to study this disease," Dr. Kleer says. So not only did Dr, Kleer gain a better understanding of CCN6, but her lab's findings open the door to a better understanding of this very challenging subtype of breast cancer. The study was published on November 7, 2016 in Oncogene. The article is titled "MMTV-cre;Ccn6 Knockout Mice Develop Tumors Recapitulating Human Metaplastic Breast Carcinomas." "Our hypothesis, based on years of experiments in our lab, was that knocking out this gene would induce breast cancer.

Chance Meeting Leads to Creation of Antibiotic Spider Silk

A chance meeting between a spider expert and a chemist has led to the development of antibiotic synthetic spider silk. After five years' work, an interdisciplinary team of scientists at The University of Nottingham (UK) has developed a technique to produce chemically functionalized spider silk that can be tailored to applications used in drug delivery, regenerative medicine, and wound healing. The Nottingham research team has shown for the first time how “click-chemistry” can be used to attach molecules, such as antibiotics or fluorescent dyes, to artificially produced spider silk synthesized by E.coli bacteria. The research, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) is published online on December 28, 2018 in Advanced Materials. The article is titled “Antibiotic Spider Silk: Site-Specific Functionalization of Recombinant Spider Silk Using “Click” Chemistry. The chosen molecules can be “clicked” into place in soluble silk protein before it has been turned into fibres, or after the fibres have been formed. This means that the process can be easily controlled and more than one type of molecule can be used to “decorate” individual silk strands. In a laboratory in the Centre of Biomolecular Sciences, Professor Neil Thomas from the School of Chemistry in collaboration with Dr. Sara Goodacre from the School of Life Sciences, has led a team of BBSRC DTP-funded Ph.D. students starting with David Harvey who was then joined by Victor Tudorica, Leah Ashley and Tom Coekin. They have developed and diversified this new approach to functionalizing “recombinant” -- artificial -- spider silk with a wide range of small molecules.