El-Solh A.A.,Medical Research |
El-Solh A.A.,State University of New York at Buffalo
Lung | Year: 2011
Pneumonia remains the leading cause of death in nursing home residents. The accumulation of dental plaque and colonization of oral surfaces and dentures with respiratory pathogens serves as a reservoir for recurrent lower respiratory tract infections. Control of gingivitis and dental plaques has been effective in reducing the rate of pneumonia but the provision of dental care for institutionalized elderly is inadequate, with treatment often sought only when patients experience pain or denture problems. Direct mechanical cleaning is thwarted by the lack of adequate training of nursing staff and residents' uncooperativeness. Chlorhexidine-based interventions are advocated as alternative methods for managing the oral health of frail older people; however, efficacy is yet to be demonstrated in randomized controlled trials. Development and maintenance of an oral hygiene program is a critical step in the prevention of pneumonia. While resources may be limited in long-term-care facilities, incorporating oral care in daily routine practice helps to reduce systemic diseases and to promote overall quality of life in nursing home residents. © 2011 Springer Science+Business Media, LLC. Source
"These data should promote a re-evaluation of those diseases to see if this new function that we've identified contributes to those defects," said senior study author Dr. Michael Buszczak, Associate Professor of Molecular Biology and with the Hamon Center for Regenerative Science and Medicine at UT Southwestern. The study, published recently in Developmental Cell, indicates that RNA-binding fox (Rbfox) proteins oversee translation of messenger RNA, or mRNA, into proteins. Using the fruit fly Drosophila as a model, researchers showed that the Rbfox1 protein, in particular, has this regulatory role. Rbfox1 proteins were known to play a key role in splicing together coding portions of genes called exons to form mRNA, which is subsequently translated to form proteins. Splicing largely takes place within the nucleus of cells, where many Rbfox1 proteins are found. But there are also variants of Rbfox1 proteins found in the cytoplasm - the portion of the cell outside the nucleus - and the function of those cytoplasmic proteins had not been understood. "We found that cytoplasmic Rbfox1 represses the production of specific proteins," Dr. Buszczak said. The lead author of the study, UT Southwestern Molecular Biology graduate student Arnaldo Carreira-Rosario, found that Rbfox1 binds to specific elements at the ends of mRNA molecules, preventing these mRNAs from being translated into proteins. If Rbfox1 proteins are lost and mRNA is no longer repressed, that could lead to aberrant growth of cells, or cancers. The researchers found that cytoplasmic forms of Rbfox1 were required for germ cell development in Drosophila. "Without this protein, the germ cells are blocked in a very specific stage of differentiation and just linger there. They can't differentiate into mature eggs," said Dr. Buszczak, an E.E. and Greer Garson Fogelson Scholar in Medical Research. This block leads to sterility in female Drosophila and, in other contexts, can result in an inappropriate proliferation of cells, which underlies cancer. Work by co-author Dr. Mani Ramaswami of Trinity College Dublin in Ireland points to a link between the newly identified function of Rbfox1 proteins and neuronal development and function, which could have important implications for a number of the neuronal disorders linked to disruption of Rbfox1. "The idea is that loss of Rbfox1 causes disease by disrupting protein expression, not RNA splicing," Dr. Buszczak said. "If this interpretation is correct, then it has implications for how one would develop therapeutics to treat the disease in question."
News Article | March 4, 2016
A study published in the prestigious journal Scientific Reports from the Nature group demonstrates, for the first time and using computational tools, that polyunsaturated lipids can alter the binding rate of two types of receivers involved in certain nervous system diseases. The work was led by members of the Research Programme on Biomedical Informatics at the IMIM (Hospital del Mar Medical Research Institute) and Pompeu Fabra University as well as researchers from the University of Tampere (Finland), and also involved scientists from the University of Barcelona.
Elite ski jumpers rely on extreme balance and power to descend the steep slopes that allow them to reach up to 100 kilometres per hour. But the US Ski and Snowboard Association (USSA) is seeking to give its elite athletes an edge by training a different muscle: the mind. Working with Halo Neuroscience in San Francisco, California, the sports group is testing whether stimulating the brain with electricity can improve the performance of ski jumpers by making it easier for them to hone their skills. Other research suggests that targeted brain stimulation can reduce an athlete’s ability to perceive fatigue1. Such technologies could aid recovery from injury or let athletes try 'brain doping' to gain a competitive advantage. Yet many scientists question whether brain stimulation is as effective as its proponents claim, pointing out that studies have looked at only small groups of people. “They’re cool findings, but who knows what they mean,” says cognitive psychologist Jared Horvath at the University of Melbourne in Australia. The USSA is working with Halo to judge the efficacy of a device that delivers electricity to the motor cortex, an area of the brain that controls physical skills. The company claims that the stimulation helps the brain to build new connections as it learns a skill. It tested its device in an unpublished study of seven elite Nordic ski jumpers, including Olympic athletes. Four times per week, for two weeks, the skiers practised jumping onto an unstable platform. Four athletes received transcranial direct-current stimulation (tDCS) as they trained; the other three received a sham procedure. The stimulation ultimately improved the athletes' jumping force by 70% and their coordination by 80%, compared with the sham group, Halo announced in February. Troy Taylor, high-performance director for the USSA, is encouraged by the results — but concedes that they are preliminary. Another study, presented on 7 March at the Biomedical Basis of Elite Performance meeting in Nottingham, UK, suggests that tDCS may reduce the perception of fatigue. Sports scientist Lex Mauger of the University of Kent in Canterbury, UK, and his colleagues found that stimulating the motor-cortex region that controls leg function allows cyclists to pedal longer without feeling tired. The researchers stimulated the brains of 12 untrained volunteers before directing the athletes to pedal stationary bicycles until they were exhausted. Every minute, they asked the cyclists to rate their level of effort. Volunteers who received tDCS were able to pedal two minutes longer, on average, than were those who were given a sham treatment. They also rated themselves as less tired. But there was no difference in heart rate or the lactate level in the muscles between the treatment and control groups. This suggests that changes in brain perception, rather than muscle pain or other body feedback, drove the improved performance. Alexandre Okano, a biological engineer at Federal University of Rio Grande do Norte in Brazil, found similar increases in cyclists’ performance when he stimulated the brain’s temporal cortex, which is involved in body awareness and in automatic functions such as breathing2. This suggests that the temporal and motor cortices are connected in ways that are not understood, or that tDCS does not target locations in the brain precisely, Okano says. These results support the notion that the brain manages exertion by collating feedback from the body and then slowing muscles to prevent fatigue, says Dylan Edwards, a neurophysiologist at Burke Medical Research Institute in White Plains, New York3. “Even when you think you’re exercising as hard as you can, there is always some reserve of ability,” he says. But Horvath cautions that little is known about the long-term effects of stimulating the brain. And others are sceptical of the technique’s potential to increase performance. Vincent Walsh, a neuroscientist at University College London, notes that the methods used in tDCS studies often differ between research groups — and might not always be optimized. For instance, the fairly intense amount of electricity that Mauger's team used has been shown to sometimes have complex and unintended effects on the brain's activity4. Replicating such experiments is difficult because of variations in how people respond to brain stimulation. Some people do not respond at all; others might respond only when stimulated in a certain way. And even an individual’s response can differ from day to day. Edwards says that it is important to map these differences if tDCS is to be used therapeutically or for other purposes. “We’re moving toward customized prescription of brain stimulation,” he says. Nonetheless, the use of tDCS in sports is only likely to increase. Stimulating the motor cortex, for instance, seems to increase dexterity, so videogamers have been quick to take up the technique. And it is increasingly easy to acquire stimulation devices; Halo has begun to market its equipment for the express purpose of increasing athletic performance. Taylor compares the use of brain stimulation by athletes to eating carbohydrates ahead of an athletic event, in the hopes of boosting endurance. “It piggybacks on the ability to learn,” he says. “It's not introducing something artificial into the body.” But Edwards worries that the availability of tDCS devices will tempt athletes to try “brain doping”, in part because there is no way to detect its use. “If this is real,” he says, “then absolutely the Olympics should be concerned about it.”
Understanding the structure of this enzyme, separase, could lead to better treatments for cancer, which occurs when cells divide out of control, said Dr. Hongtao Yu, Professor of Pharmacology and a Howard Hughes Medical Institute (HHMI) Investigator at UT Southwestern. "Chromosomes contain the genetic blueprint for life, and must be precisely duplicated and equally partitioned during each cell division. The cohesin complex forms a molecular ring to encircle the duplicated chromosomes and tether them together until the moment of chromosome separation," said Dr. Yu, senior author of the study published online in Nature. "In organisms from fungi to humans, separase - an enzyme that breaks down proteins - cleaves and opens the cohesin ring to allow chromosome separation and subsequent partition into the two new daughter cells." Despite its central role in cell biology, the atomic structure of separase has eluded scientists since its discovery nearly two decades ago. This situation left a void in the understanding of the enzyme's mechanism and regulation, the researchers said. "We determined the atomic structure of separase from a fungus that can grow at high temperatures. The structure reveals how separase recognizes and cleaves the cohesin ring, allowing the chromosomes to separate," said Dr. Yu, a Michael L. Rosenberg Scholar in Medical Research and member of the Harold C. Simmons Comprehensive Cancer Center at UT Southwestern. "This particular protein is very unstable in species that grow at normal temperature, such as human body temperature, but was more stable in the high-temperature fungus that we studied." Because of the enzyme's role in cell division, chemical inhibitors of separase are expected to block cell proliferation and therefore may have therapeutic value in treating cancer. "The fungal separase that we studied is very similar to human separase. For that reason, we believe our structure will aid in the design of such inhibitors," he said, "because once you have the shape of the structure, you can computationally look for molecules that will bind to it." Study co-authors included Dr. Zhonghui Lin, a research specialist at the HHMI and in the Department of Pharmacology, and Dr. Xuelian "Sue" Luo, Associate Professor of Pharmacology and Biophysics. Explore further: New key mechanism in cell division discovered More information: Structural basis of cohesin cleavage by separase, Nature, DOI: 10.1038/nature17402