Credit Newswise — If you have trouble sleeping, the neurons in your brain may be firing like those in roundworms randomly seeking food in the absence of clues, says University of Oregon biologist Shawn R. Lockery. That connection is proposed in a theoretical neuroscience paper co-authored by 12 researchers at 10 institutions that is in the journal eLife. The research -- 14 years in the making -- was led by Lockery and supported by the National Institutes of Health. As humans sleep, neurons fire randomly in between brief, alternating states of wakefulness and sleep. Such fragmentation is heightened in sleep disorders. The fragmentation as seen in the worms -- the nematode Caenorhabditis elegans -- offers a new framework to identify genetic and physiological underpinnings of the neural circuitry involved in sleep, the research team concluded. The nematode brain is the smallest known to science, containing just 302 neurons and making it a simple model from which to gather basic information, Lockery said. "Our field has a complete wiring diagram of this worm's brain," said Lockery, a member of the UO Institute of Neuroscience. "You can find the same neuron in any animal you look into and learn to understand how individual neurons function." Researchers in Lockery's lab tested the predictability of mathematically driven equations about random search strategies in the brain. To do so, the worms were removed from access to their usual food -- bacteria in rotting vegetables -- and placed on clean petri dishes with no sensory clues as to where a meal is located. Initially, the movements of the worms and the neural networks involved were mapped as the worms crawled forward, paused, reversed, and then resumed their search in another direction. "Every animal faces the need to find food," Lockery said. "In some instances food is undetectable until you basically fall on it: birds looking for marine invertebrates in the sand will move about and peck until they find their meal. This is called random search." Humans, too, from hunter-gatherers to those who engage in technologically advanced fishing, exhibit similar random-search behaviors but, "no one has known how the nervous system controls this," Lockery said. With the mapping done, researchers used lasers to knock out neurons. They expected the worms to spend more time in reverse when neurons linked to forward movement were eliminated, or vice versa. Instead, the reaction was symmetrical. Shorter times were found in both forward and reverse movements. "There are centers in the human brain stem that promote wakefulness and sleep," Lockery said. "They are coupled just like the system we see in the worms. This involves clusters of neurons that are fighting against each other to be active. We constantly wake up and go back to sleep, but we don't remember it. Sleep is random, just the way the worm's movement is." Researchers have done similar experiments in rats and mice where neurons related to sleep states were manipulated. The findings are consistent. "The same paradoxical effect that we found in our worms also occurs in these other organisms," Lockery said. "This line of research suggests that we now have a simple way to try to understand how this fragmentation occurs. That's the first step in understanding how medical science might be able to pursue therapeutics that could mitigate extreme cases of fragmentation."
Credit Newswise — A fungal disease that poses a serious threat to cacao plants - the source of chocolate - reproduces clonally, Purdue University researchers find. The fungus Moniliophthora roreri causes frosty pod rot, a disease that has decimated cacao plantations through much of the Americas. Because M. roreri belongs to a group of fungi that produces mushrooms - the fruit of fungal sex - many researchers and cacao breeders believed the fungus reproduced sexually. But a study by Purdue mycologists Catherine Aime and Jorge Díaz-Valderrama shows that M. roreri generates billions of cocoa pod-destroying spores by cloning, even though it has two mating types - the fungal equivalent of sexes - and seemingly functional mating genes. The findings could help improve cacao breeding programs and shed light on the fungal mechanisms that produce mushrooms. "This fungus is phenomenally unusual - it has mating types but doesn't undergo sexual reproduction," said Díaz-Valderrama, doctoral student in mycology. "This knowledge is biologically and economically valuable as we seek better insights into how mushrooms come about and how we can reduce this disease's damage to the cocoa industry." Cocoa is one of the few major crops produced almost entirely by small farms, and the instability of cocoa prices often makes fungicides a risky investment for growers. Instead, many growers opt to regularly monitor their crop for symptoms of frosty pod rot, burying pods that display the telltale dark lesions or white dusting to prevent further dispersal of fungal spores. Over the last 60 years, the disease has spread - likely through unwitting transportation of infected pods - through much of South America, all of Central America and into Mexico. Frosty pod rot has dropped cocoa yields in some areas by up to 100 percent, forcing many growers to abandon their plantations altogether. Brazil is the only cocoa-producing country in the continental Americas untouched by frosty pod rot, whose pernicious effects have spurred the majority of global cacao production to relocate to West Africa. These regions remain highly vulnerable to the disease, Díaz-Valderrama said. Understanding the fundamental biology of the fungus could help disease control efforts, but researchers have long been stumped by M. roreri's reproductive habits, which seem to deviate from those of sister species. Fungal reproduction is complicated. Instead of male and female sexes, fungi can have a vast number of different mating types, leading to a wide and varied range of potential mates - up to 20,000 in some species. But many fungi also reproduce clonally under favorable conditions, simply copying their genome and producing billions of offspring. Digging into the genomics and population genetics of M. roreri, Aime and Díaz-Valderrama found indications that the fungus might be able to sexually reproduce: It has two seemingly compatible mating types and what appear to be functional sex pheromone receptors. But they couldn't find any evidence that the mating types were recombining in the field or lab, and no records of M. roreri mushrooms exist - signs that the fungus has ditched sexual reproduction in favor of cloning. "Fungi usually start reproducing via cloning when they're very well suited for their environment," said Aime, associate professor of mycology. "In terms of resources, sex is expensive while cloning is a cheap and easy way to produce a lot of offspring." The researchers found both mating types in South America and only one type in Central America. This supports the hypothesis that the disease originated in South America and was more recently introduced into Central America where it rapidly spread through clonal reproduction. The study also shows that what some researchers believed to be different varieties of the fungus are actually genetic variations in the two mating types. The findings open the door for breeding programs to investigate which mating type is more virulent and possibly develop resistant cacao cultivars. In the meantime, chocolate lovers should stay calm, Díaz-Valderrama said. "We're working on identifying biochemical components that could be useful for controlling frosty pod rot and protecting vulnerable cacao-growing regions."
Credit Newswise — New research looks into the paradox that women who sunbathe are likely to live longer than those who avoid the sun, even though sunbathers are at an increased risk of developing skin cancer. An analysis of information on 29,518 Swedish women who were followed for 20 years revealed that longer life expectancy among women with active sun exposure habits was related to a decrease in heart disease and noncancer/non-heart disease deaths, causing the relative contribution of death due to cancer to increase. Whether the positive effect of sun exposure demonstrated in this observational study is mediated by vitamin D, another mechanism related to UV radiation, or by unmeasured bias cannot be determined. Therefore, additional research is warranted. "We found smokers in the highest sun exposure group were at a similar risk as non-smokers avoiding sun exposure, indicating avoidance of sun exposure to be a risk factor of the same magnitude as smoking," said Dr. Pelle Lindqvist, lead author of the Journal of Internal Medicinestudy. "Guidelines being too restrictive regarding sun exposure may do more harm than good for health."
Credit Newswise — Women can choose from a wide selection of birth control methods, including numerous oral contraceptives, but there’s never been an analogous pill for men. That’s not for lack of trying: For many years, scientists have attempted to formulate a male pill. Finally, a group of researchers has taken a step toward that goal by tweaking some experimental compounds that show promise.The researchers present their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics. One compound that’s been studied as a potential male contraceptive is testosterone. “At certain doses it causes infertility,” says Jillian Kyzer, a graduate student working on the topic. “But at those doses, it doesn’t work for up to 20 percent of men, and it can cause side effects, including weight gain and a decrease in ‘good’ cholesterol.” Bringing any male contraceptive to market requires it to satisfy several requirements, explains Kyzer’s team leader, Gunda I. Georg, Ph.D., who is based at the University of Minnesota College of Pharmacy. It would have to be soluble so it could be taken by mouth. It would start working fairly quickly, and it wouldn’t diminish libido. It would be safe even if taken for decades. And because some users would eventually want to have children, its impact on fertility would be reversible, with no lingering ill effects on sperm or embryos. “That’s a very high bar for bringing a male contraceptive to market,” Georg points out. These hurdles have driven many investigators from the hunt, yet Georg’s team perseveres. “It would be wonderful to provide couples with a safe alternative because some women cannot take birth control pills,” she says. Drug companies, including Bristol-Myers Squibb (BMS), have created some experimental male contraceptives, but these too have drawbacks, Kyzer says. For instance, one of the company’s test compounds is good at inhibiting fertility but isn’t very soluble, so it can’t be taken by mouth. “No one wants to inject themselves with a needle once a day or once a week for most of their lives,” she notes. Another Bristol-Myers Squibb experimental compound can be taken orally but isn’t very selective in terms of its cellular targets in the body. That means the compound not only interacts with the retinoic acid receptor-α, which is involved in male fertility, but also with two other retinoic acid receptors that are unrelated to fertility. That flaw could cause side effects. Kyzer and several of her colleagues are creating numerous substances that are similar in their chemical structure to the Bristol-Myers Squibb compounds. Although the optimal contraceptive for men remains elusive, Georg’s team has made some progress. For example, the researchers are gaining a better understanding of how tweaks to the chemical structure of their test compounds affect the substances’ cellular interactions in the body. One of those tweaks added a polar group to the molecule, which made the test compounds more soluble. Another tweak replaced an amide bond in the BMS compound with slightly different bonds that are known in the field of medicinal chemistry to mimic an amide bond. As intended, that change improved the test compounds’ stability, meaning they would last longer in the body. Unfortunately, both types of modifications also reduced the specificity of the compounds for the intended retinoic acid receptor-α target. The group continues to refine the chemical structures to achieve the ultimate balance of solubility, specificity and stability as they aim to design a better male pill. They are now investigating hybrid compounds that incorporate scaffolds and structural features from several other compounds known to interact with the retinoic acid receptor. The researchers acknowledge funding from the Contraception Research Branch, Eunice Kennedy Shriver National Institute of Child Health & Human Development.
Credit Newswise — The first time back to the gym after a long break usually results in sore muscles. Fortunately, the return trip a few days later--if it happens--is generally less painful. Scientists have studied this reduced-soreness phenomenon for decades and even have a name for it--the repeated bout effect. Despite all those years of research, they still can't figure out exactly why people feel less sore the second time around. What they do know is the immune system plays some role in how the muscle repairs itself and protects against additional damage. But now exercise science researchers at BYU have produced evidence that shows for the first time the surprising presence of very specific immune workers: T-cells. "You think of T-cells as responding to infections, not repairing muscles--but we found a significant accumulation of T-cells infiltrating damaged muscle fibers," said Robert Hyldahl, assistant professor of exercise science at BYU. "Our study is the first to show T-cells present in human muscle in response to exercise-induced damage." The research appears this month in Frontiers in Physiology and builds off past studies that implicate immune cells in muscle healing. One such study was a 2013 paper out of Harvard showing T-cells active in the skeletal muscles of mice (but not yet humans) after injury. For the study, researchers, put 14 men and women through two vigorous rounds of exercise on an isokinetic dynamometer machine, 28 days apart. ("All of them got really sore," Hyldahl said.) Before and after each bout of exercise, the team took muscle biopsies from the subjects and then used immunohistochemistry and microscopy to analyze the muscle tissue. The BYU group found an expected increase in certain white blood cells after the second bout of exercise, but only identified the T-cells after it was suggested by Amanda Gier, one of two undergraduate coauthors on the paper, who was enrolled in an immunology course at the time. "T-cells, up until recently, were not thought to enter healthy skeletal muscle," said lead author and grad student Michael Deyhle. "We hadn't planned on measuring them because there's no evidence that T-cells play a role in infiltrating damaged muscle tissue. It's very exciting." The presence of the T-cells suggests that muscles become more effective at recruiting immune cells following a second bout of exercise and that these cells may facilitate accelerated repair. In other words, the muscle seems to remember the damaging insult and reacts similarly to when the immune system responds to antigens--toxins, bacteria or viruses. The group was also surprised to find inflammation actually increased after the second round of exercise. Hyldahl, his students and many physiologists have long thought inflammation goes down after the second bout of exercise, contributing to that "less sore" effect. Instead, the slightly enhanced inflammatory response suggests inflammation itself probably does not worsen exercise-induced muscle damage. "Many people think inflammation is a bad thing," Deyhle said. "But our data suggest when inflammation is properly regulated it is a normal and healthy process the body uses to heal itself." Adds Hyldahl: "Some people take anti-inflammatory drugs such as Ibuprofen and Aspirin after a workout, but our study shows it may not actually be effective. The inflammation may not be directly causing the pain, since we see that muscle soreness is reduced concurrent with increases in inflammation."
Credit Newswise — A new study shows that a variety of physical activities from walking to gardening and dancing can improve brain volume and cut the risk of Alzheimer's disease by 50%. This research, conducted by investigators at UCLA Medical Center and the University of Pittsburgh, is the first to show that virtually any type of aerobic physical activity can improve brain structure and reduce Alzheimer's risk. The study, funded by the National Institute of Aging, was published on March 11 in the Journal of Alzheimer's Disease. The researchers studied a long-term cohort of patients in the 30-year Cardiovascular Health Study, 876 in all, across four research sites in the United States. These participants had longitudinal memory follow up, which also included standard questionnaires about their physical activity habits. The research participants, age 78 on average, also had MRI scans of the brain analyzed by advanced computer algorithms to measure the volumes of brain structures including those implicated in memory and Alzheimer's such as the hippocampus. The physical activities performed by the participants were correlated to the brain volumes and spanned a wide variety of interests from gardening and dancing to riding an exercise cycle at the gym. Weekly caloric output from these activities was summarized. The results of the analysis showed that increasing physical activity was correlated with larger brain volumes in the frontal, temporal, and parietal lobes including the hippocampus. Individuals experiencing this brain benefit from increasing their physical activity experienced a 50% reduction in their risk of Alzheimer's dementia. Of the roughly 25% in the sample who had mild cognitive impairment associated with Alzheimer's, increasing physical activity also benefitted their brain volumes. Said lead author Cyrus A. Raji, MD, PhD, of UCLA, "This is the first study in which we have been able to correlate the predictive benefit of different kinds of physical activity with the reduction of Alzheimer's risk through specific relationships with better brain volume in such a large sample." George Perry, PhD, Editor in Chief of Journal of Alzheimer's Disease, added, "Currently the greatest promise in Alzheimer's disease research is lifestyle intervention including increased exercise. Raji et al present a landmark study that links exercise to increases in grey mater and opens the field of lifestyle intervention to objective biological measurement." According to the Alzheimer's Association, Alzheimer's disease currently affects 5.1 million Americans and is projected to increase to13.8 million over the next 30 years. Dr. Raji commented, "We have no magic bullet cure for Alzheimer's disease. Our focus needs to be on prevention."
Credit Newswise — Researchers from The University of Texas Medical Branch at Galveston have found that women who take the birth control pill, which lessen and stabilize estrogen levels, were less likely to suffer serious knee injuries. The findings are currently available in Medicine & Science in Sports & Exercise, the official journal of the American College of Sports Medicine. Female athletes are 1.5 to 2 times more likely than their male counterparts to injure their anterior cruciate ligament, or ACL. The ACL is a ligament that connects the top and bottom portions of the knee. Damage to this ligament is a serious athletic injury that can be career altering. Return-to-play rates after ACL injury are as low as 49 percent among soccer players. Also, this injury may lead to lifelong issues with knee instability, altered walking gait and early onset arthritis. Using a national insurance claims and prescription database of 23,428 young women between 15 and 19, the study found that women with an ACL knee injury who were taking the birth control pill were less likely to need corrective surgery than women of the same age with ACL injuries who do not use the birth control pill. Researchers have proposed that the female hormone estrogen makes women more vulnerable to ACL injury by weakening this ligament. A previous investigation found that more ACL injuries in women occur during the points of their menstrual cycle when estrogen levels are high. "Birth control pills help maintain lower and more consistent levels of estrogen, which may prevent periodic ACL weakness," said lead author and M.D. - Ph.D. student Aaron Gray. "With this in mind, we examined whether oral contraceptive use protected against ACL injuries that require surgery in women." Women between15-19 y in need of ACL reconstructive surgery, the age group with the highest rates of ACL injuries by a wide margin, were 22 percent less likely to be using the birth control pill than non-injured women of the same age. Gray said that puberty might explain the high number of ACL injury cases in young women of this age. During puberty, there is a sharp rise in estrogen levels as well as growth spurts in the legs. Following one of these growth spurts, it takes time for the adolescent to develop good coordination with their newly elongated limbs. "Young athletes currently use birth control pills for various reasons including more predictable cycles and lighter periods," Gray said. "Injury risk reduction could potentially be added to that list with further, prospective investigations."
DALLAS – A surgical team at Baylor University Medical Center at Dallas successfully performed a heart transplant on a patient they were keeping alive with a total artificial heart, a portable device that pumps blood throughout the body when both sides of the heart fail. The heart transplant was performed February 29. Weeks earlier, Baylor University Medical Center surgeons had removed the patient's damaged native heart and replaced it with a total artificial heart. The lifesaving technology is used as a "bridge" for patients who have end-stage biventricular heart failure and are waiting for a donor human heart or who are too sick to receive a transplant. It provides mechanical support until a donor human heart can be found. Baylor University Medical Center at Dallas is the only hospital in the region to implant a total artificial heart and transition the patient to a successful heart transplant. The center joins select group of high volume transplant centers across the country to offer this service for patients. "This is a special day for our patient and for our entire team," said Shelley Hall, MD, chief of transplant cardiology, mechanical circulatory support and heart failure, Baylor University Medical Center at Dallas. "The patients who need this technology are the sickest of the sick and we are proud to offer our patients the latest tool to battle the nation's number one killer, heart disease." The patient, 52-year-old Bryan Tyo, is a McKinney resident who suffered a heart attack in January. The damage to his heart was so advanced that repair surgery and other mechanical assist devices could not help. "Baylor now offers every option for our heart failure patients," said Themistokles Chamogeorgakis, MD, associate surgical director of heart transplantation and mechanical circulatory support, Baylor University Medical Center at Dallas. "With fewer donor hearts becoming available, it is critical to offer these opportunities to bridge our patients to transplant." Tyo is the first patient in North Texas to use the SynCardia Total Artificial Heart Freedom driver. It is a 13.5-pound portable unit that powered his artificial heart. The device replaced both failing ventricles and the four heart valves, restored an immediate flow of blood to the body and helped vital organs recover faster. "I'm just thankful for this second chance at life," said Tyo. "My wife and I celebrated our 25th anniversary in October and I've got 25 more years to be with her, if she'll put up with me," he joked. Heart disease is the number one cause of death in the United States, claiming the lives of nearly 600,000 people a year. The bridge to transplant option is critical because only 2,200 donor hearts become available every year in the U.S. While wait times can vary, Baylor University Medical Center has a median wait time of seven days for status 1A heart transplant patients from the time they are listed to transplant, one of the shortest wait times in the country.
Credit Newswire — Athletes, the elderly and others who suffer from injuries and arthritis can lose cartilage and experience a lot of pain. Researchers are now reporting, however, that they have found a way to produce cartilage tissue by 3-D bioprinting an ink containing human cells, and they have successfully tested it in an in vivo mouse model. The development could one day lead to precisely printed implants to heal damaged noses, ears and knees. The researchers presented their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics. A brand-new video on the research is available at http://bit.ly/ACS3DPrint. "Three-dimensional bioprinting is a disruptive technology and is expected to revolutionize tissue engineering and regenerative medicine," says Paul Gatenholm, Ph.D. "Our team’s interest is in working with plastic surgeons to create cartilage to repair damage from injuries or cancer. We work with the ear and the nose, which are parts of the body that surgeons today have a hard time repairing. But hopefully, they’ll one day be able to fix them with a 3-D printer and a bioink made out of a patient’s own cells." Gatenholm’s team at the Wallenberg Wood Science Center in Sweden is tackling this challenge step by step. First, they had to develop an ink with living human cells that would keep its shape after printing. Previously, printed materials would collapse into an amorphous pile. To create a new bioink, Gatenholm’s team mixed polysaccharides from brown algae and tiny cellulose fibrils from wood or made by bacteria, as well as human chondrocytes, which are cells that build up cartilage. Using this mixture, the researchers were able to print living cells in a specific architecture, such as an ear shape, that maintained its form even after printing. The printed cells also produced cartilage in a laboratory dish. "But under in vitro conditions, we have to change the nutrient-filled liquid that the material sits in every other day and add growth factors," Gatenholm says. "It’s a very artificial environment." So the next step was to move the research from a lab dish to a living system. Gatenholm’s team printed tissue samples and implanted them in mice. The cells survived and produced cartilage. Then, to boost the number of cells, which is another hurdle in tissue engineering, the researchers mixed the chondrocytes with human mesenchymal stem cells from bone marrow. Previous research has indicated that stem cells spur primary cells to proliferate more than they would alone. Preliminary data from in vivo testing over 60 days show the combination does indeed encourage chondrocyte and cartilage production. Gatenholm says further preclinical work needs to be done before moving on to human trials. To ensure the most direct route, he is working with a plastic surgeon to anticipate and address practical and regulatory issues. In addition to cartilage printing, Gatenholm’s team is working with a cosmetic company to develop 3-D bioprinted human skin. Cosmetic companies are now prohibited in Europe from testing cosmetics on animals, so they hope to use printed skin to try out makeup, anti-wrinkling techniques and strategies to prevent sun damage.
Credit Newswise — Drug therapies for many conditions end up treating the whole body even when only one part — a joint, the brain, a wound — needs it. But this generalized approach can hurt healthy cells, causing nasty side effects. To send drugs to specific disease locations and avoid unwanted symptoms, researchers developed cellular "backpacks" that are designed to carry a therapeutic cargo only to inflamed disease sites. The researchers present their work today at the 251st National Meeting & Exposition of the American Chemical Society (ACS). ACS, the world’s largest scientific society, is holding the meeting here through Thursday. It features more than 12,500 presentations on a wide range of science topics. "What we want to do is take advantage of immune cells whose job it is to seek out disease in the body, and use them to deliver cargo for us," says Roberta Polak, a postdoctoral research associate. "How do we do that? Our lab developed cellular backpacks that can be loaded with therapeutic compounds and unloaded." Polak and fellow researchers in the Massachusetts Institute of Technology (MIT) labs of Michael Rubner, Ph.D., and Robert Cohen, Ph.D., make the backpacks by stacking ultra-thin layers of polymer materials on top of each other. According to Rubner, they could be used to treat a wide range of diseases from cancer to Parkinson’s. The resulting pack has different functional regions. One is Velcro-like, attaching via antibody-antigen binding to immune cells, such as monocytes and macrophages. These are the body’s defense cells that travel to sites of inflammation — a natural reaction to infection and disease — and gobble up foreign invaders or attack cancer cells. In vitro testing has shown that the backpacks can stick to the surfaces of the immune cells without getting engulfed. In collaboration with the group of Samir Mitragotri at the University of California at Santa Barbara, the MIT team has also demonstrated in mice that these backpack-functionalized immune cells accumulate in locations where inflammation — a sign of disease — occurs. But there was a problem. The medicine they were using to test the backpacks, a cancer drug called doxorubicin, was leaking out — even during the initial fabrication process. So Polak worked on this part of the backpack, its payload region. To stop the premature release of the drug, she trapped it in liposomes, tiny bubbles that have already been used to carry therapeutic compounds for other delivery systems, and then incorporated them into the backpacks. She found that she could fit nine times the amount of doxorubicin in the liposomes than in the backpacks alone, potentially transforming them into an even more potent weapon. To control the release of the drug payload, Polak used liposomes that are echogenic, or sensitive to ultrasound. So in principle, when backpacks infused with these bubbles reach their destination, they can be burst open with ultrasound waves. Now, to see how well they work to treat a specific disease, Polak is collaborating with Elena Batrakova, Ph.D., at the University of North Carolina at Chapel Hill. Batrakova has been working with mice to develop new treatments for brain inflammation, a characteristic of diseases such as Parkinson’s and Alzheimer’s. They want to see if they can use the backpacks to carry an inflammation-fighting enzyme across the blood-brain barrier.