Newswise —  Washing those dreadful dishes after a long day seems like the furthest thing from relaxation. Or is it? Student and faculty researchers at Florida State University have found that mindfully washing dishes calms the mind and decreases stress. Published in the journal Mindfulness, the study looked at whether washing dishes could be used as an informal contemplative practice that promotes a positive state of mindfulness — a meditative method of focusing attention on the emotions and thoughts of the present moment. “I’ve had an interest in mindfulness for many years, both as a contemplative practitioner and a researcher,” said Adam Hanley, a doctoral candidate in FSU College of Education’s Counseling/School Psychology program and one of the study’s authors. “I was particularly interested in how the mundane activities in life could be used to promote a mindful state and, thus, increase overall sense of well-being.” After conducting a study with 51 students, the researchers found that mindful dishwashers — those who focused on the smell of the soap, the warmth of the water, the feel of the dishes — reported a decrease in nervousness by 27 percent and an increase in mental inspiration by 25 percent. The control group, on the other hand, didn’t experience any benefits. The research team also included Alia Warner and Vincent Delhili, doctoral candidates at Florida State; Angela Canto, assistant professor at Florida State; and Eric Garland, associate professor at University of Utah. ###  
Newswise — A Case Western Reserve University School of Medicine team received $2 million from the Patient-Centered Outcomes Research Institute (PCORI) to study a combination approach to help patients stop smoking, particularly those who are socially and economically disadvantaged. The project involves partnership with faculty and staff at MetroHealth Medical Center, the Ohio Department of Health and National Jewish Health, the Quitline providers for Ohio. The study team, led by Susan Flocke, PhD, will determine whether pairing the Teachable Moment Communication Process (TMCP) with the Ask-Advise-Connect (AAC) strategy will bolster smoking cessation outcomes. The AAC approach focuses on a systems-based strategy for identifying routinely the smoking status of patients, providing brief advice and offering a referral to the Quitline, a hotline staffed by professionals trained in smoking cessation counseling. This study will implement changes in the electronic health record to allow an electronic referral so that patients who want smoking cessation assistance are contacted proactively by the Quitline. TMCP, on the other hand, uses a communication strategy developed by Flocke’s team that incorporates the patient’s concerns into a clinician partnership-oriented discussion about stopping tobacco use. The problem with AAC alone is that many patients referred to the Quitline are not ready to stop smoking, but they may feel obligated to accept the referral to the hotline from their primary care team. In prior studies, less than 50 percent of patients who agreed to be referred to Quitline were successfully contacted by its counselors, even after five call attempts. However, among those who are contacted, enrollment and engagement in counseling services are good and have a positive effect on cessation attempts. By combining TMCP with AAC, the goal is to increase the numbers of patients referred to Quitline who are truly committed to smoking cessation and therefore more likely to enroll and benefit from tailored counseling. Investigators will pay particular attention to improving how smoking cessation advice and assistance are delivered to socially and economically disadvantaged patients. The Case Western Reserve research team will conduct a randomized trial of the TMCP and AAC combo in eight clinics serving more than 25,000 patients who smoke. Data will be collected through patient surveys, electronic health records, and Quitline participation. Additionally, the study will involve in-depth interviews with subgroups of patients to learn ways to improve their referral to the Quitline. “Research has shown that economically and socially disadvantaged individuals are more likely to smoke and less likely to use smoking cessation services,” said Flocke, Associate Professor, Department of Family Medicine & Community Health and Associate Director of the Prevention Research Center, Case Western Reserve University School of Medicine. “With our research, we plan to systematically create linkages between primary care clinics and community resources to increase smoking cessation services to those people who are least likely to access them.” “This project was selected for PCORI funding not only for its scientific merit and commitment to engaging patients and other stakeholders, but also for its potential to fill an important gap in our health knowledge and give people information to help them weigh the effectiveness of their care options,” said PCORI Executive Director Joe Selby, MD, MPH. “We look forward to following the study’s progress and working with Case Western Reserve University School of Medicine to share the results.” Flocke’s study was selected for PCORI funding through a highly competitive review process in which patients, clinicians, and other stakeholders joined clinical scientists to evaluate the proposals. Applications were assessed for scientific merit, how well they will engage patients and other stakeholders, and their methodological rigor among other criteria. The award to Flocke has been approved pending completion of a business and programmatic review by PCORI staff and issuance of a formal award contract. PCORI is an independent, nonprofit organization authorized by Congress in 2010. Its mission is to fund research that will provide patients, their caregivers, and clinicians with the evidence-based information needed to make better-informed healthcare decisions. For more information about PCORI’s funding, visit
Newswise — Vampires may want your blood for the sake of their longevity, but have you ever wondered why your doctor is also interested in it? Well, unlike the vampire who draws blood for his own benefit, a doctor is interested in your blood for the good of your health. “Blood carries many secrets about your health,” says Karen Rizzo, MD, 2015 president of the Pennsylvania Medical Society and a practicing physician in Lancaster. “Through your blood, physicians can have a better understanding of your health as blood tests can help find potential problems early.” One such problem that worries physicians is heart disease. And, through blood tests, physicians can look inside your body to learn if you’re at risk or not. So, it’s not unusual for a physician to order a lipid panel to measure total cholesterol and triglycerides. It’s a common test given to determine the risk of heart disease. The total cholesterol is divided into two subclasses, which are called high-density lipoprotein (HDL) and low-density lipoprotein (LDL). Science has proven that the lower your LDL, triglycerides, and total cholesterol, the lower your risk of heart disease. People with heart disease tend to have elevated cholesterol, especially LDL and triglycerides. “Cholesterol is important piece of your health puzzle,” says Pennsylvania Academy of Family Physicians President Nicole Davis, MD, who practices in Wyncote. “Keeping it in check and under control can lead to longer, healthier lives, while abnormal numbers can be traced to serious issues like heart attack and stroke.” In Pennsylvania it’s no laughing matter. According to the Pennsylvania Department of Health, heart disease is the number one killer of Pennsylvanians. Stroke ranks up there too and is the third leading cause of death in women, and fifth for men. On an average day in 2010, there were 86 deaths due to heart disease and 18 deaths due to stroke. For that year, 31,274 Pennsylvanians died due to heart disease, representing 25.3 percent of all deaths. In that same year, 6,629 or 5.4 percent of deaths in Pennsylvania were the result of a stroke. Certain blood tests are also used to detect signs of cancer, although patients should not jump to conclusions if their physician orders a cancer blood test. Diagnosing a patient can be a process of elimination to find exactly what is wrong. But a complete blood count (CBC) is a common blood test that a doctor may recommend to help diagnose leukemia and lymphoma. It may also be used with current cancer patients to see if cancer has spread to bone marrow or to determine how a person is handling treatment. Most recently, Science Translational Medicine, a medical journal from the American Association for the Advancement of Science, published an article that reported a new blood test could help detect a relapse of breast cancer. This blood test uses a technique called mutation tracking and has been making national headlines. “It’s exciting to learn of these types of advancements, and as we’ve known for many other diseases, blood can tell us a lot about a patient,” says Margaret A. O’Grady, RN, MSN, OCN, who is currently president of the Pennsylvania Society of Oncology & Hematology. According to state statistics from the Pennsylvania Cancer Incidence and Mortality 2012 Executive Summary, there were 10,652 cases of female breast cancer in Pennsylvania. Another blood test is the prostate-specific antigen (PSA) blood test. This test is used to look for warning signs of prostate cancer; however, this detection test can’t fully tell a physician if a man has cancer. But, if the results are at a level that may be of a concern to the physician, this test could lead to a physician to order a biopsy. According to Cancer Facts and Figures, Pennsylvania 2014, prostate cancer was the third most common cancer in the Keystone State behind lung and breast. Fortunately, the age-adjusted rates of prostate cancer in Pennsylvania as well as the country showed a decreasing trend from 2001 to 2011 while the Pennsylvania rate was lower than the national rate. “It’s very clear that early detection plays an important role in beating any type of cancer,” says O’Grady. “Blood tests can and do play a role in early detection for many patients of certain types of cancer.” For those planning to have a baby, expect your physician to also be interested in your blood during pregnancy. For pregnant women, a blood test might be used to monitor potential problems such as anemia, or diagnosis of possible infections such as toxoplasmosis. Toxoplasmosis is harmless to the pregnant woman, but it may cross the placenta and cause harm to the baby. “It’s important for a mother-to-be to pay close attention to their health during pregnancy,” says Kurt T. Barnhart, MD, FACOG, who is currently the chair of the Pennsylvania Section of the American Congress of Obstetricians and Gynecologists. “Women should see their physician throughout pregnancy for the safety of both themselves and their baby,” says Dr. Barnhart, who practices in Philadelphia. “Blood tests can be expected periodically.” Finally, when it comes to blood, the Pennsylvania Medical Society says community members should consider becoming blood donors. According to the organization, there’s no substitute for human blood and one pint of donated blood could save as many as four lives. This news release is brought to you by the Pennsylvania Health News Service Project, consisting of 21 Pennsylvania-based medical and specialty associations and societies. Members of PHNS include Pennsylvania Allergy & Asthma Association, Pennsylvania Dental Association, Pennsylvania Academy of Dermatology & Dermatologic Surgery, Pennsylvania Academy of Ophthalmology, Pennsylvania Academy of Otolaryngology, Pennsylvania Academy of Family Physicians, Pennsylvania American Congress of Obstetricians and Gynecologists, Pennsylvania Chapter of the American College of Cardiology, Pennsylvania Chapter of the American College of Emergency Physicians, Pennsylvania Chapter of the American College of Physicians, Pennsylvania Chapter of the American Academy of Pediatrics, Pennsylvania Medical Society Alliance, Pennsylvania Medical Society, Pennsylvania Neurosurgical Society, Pennsylvania Orthopaedic Society, Pennsylvania Psychiatric Society, Pennsylvania Society of Anesthesiologists, Pennsylvania Society of Gastroenterology, Pennsylvania Society of Oncology & Hematology, Robert H. Ivy Society of Plastic Surgeons, and Urological Association of Pennsylvania. Inquiries about PHNS can be directed to Chuck Moran via the Pennsylvania Medical Society at (717) 558-7820,, or via Twitter @ChuckMoran7.
Newswise — RPB-supported researchers have made a significant discovery that might lead to the delay or prevention of the most common cause of blindness in the elderly: age-related macular degeneration (AMD). Patients who take the drug L-DOPA (for Parkinson Disease, Restless Legs or other movement disorders) are significantly less likely to develop AMD and, if they do, it is at a significantly later age. "There are only limited and highly invasive therapies for those with AMD and no known preventative treatment," said Brian S. McKay, PhD, Department of Ophthalmology and Vision Science, University of Arizona. "Our findings imply that L-DOPA may be repurposed to prevent or delay AMD." Here's how the multi-institution team of scientists made the discovery. The investigators had been conducting basic research into albinism, which causes profound vision loss and changes in the structure of the eye, especially the retina, and specifically the macula, the area of the retina that is associated with central vision lost in AMD. The retina pigment epithelium is a critical support layer of tissue in the retina that fosters macula development and keeps it healthy through L-DOPA signaling. L-DOPA is made in pigmented tissues, and it has been known for a long time that lower risk for AMD is associated with darker pigmentation; Blacks have a five-fold lower risk for AMD than Whites. The researchers postulated that signaling through the L-DOPA receptor may underlie racial disparities in AMD incidence. To test this, they examined the health records of 37,000 patients at the Marshfield Clinic for individuals with AMD, or those taking L-DOPA, or those with both AMD and taking L-DOPA. In patients who were given L-DOPA before being diagnosed with AMD, their AMD was diagnosed 8 years later than those not taking L-DOPA. These results were then confirmed in a much larger data set of 87 million patients, and the study was expanded to include prevention and delay of "wet" AMD, the most devastating form of the disease. "Developing a new drug costs more than $2 billion and takes 13.5 years from discovery to market. Drug repositioning does not require anywhere near those costs," said lead author Murray Brilliant, PhD, Director at the Center for Human Genetics at the Marshfield Clinic Research Foundation. "Our methods illustrate the power of precision medicine research -- using the electronic medical records of large numbers of patients -- to test unexpected drug interactions and find new uses for old drugs." "The results suggest a new path forward in our fight against AMD that may even include a strategy to prevent those at risk of the disease from ever developing it," McKay said. "In the end, L-DOPA may not be the drug that ends the disease, but the pathway identified here is likely to be a key observation as the search for a cure continues." This work was supported by Translational Sciences, The National Human Genome Research Institute, Research to Prevent Blindness, Bright Focus, The Edward N. & Della L. Thome Memorial Foundation, the Wisconsin Genomics Initiative, National Eye Institute, the Marshfield Clinic and the University of Arizona.
Newswise — People with epilepsy experience uncontrolled seizures that can impair quality of life and cause stigma that leads to social isolation. The neurological condition can limit some activities most people take for granted, such as sustaining work or operating a vehicle. Researchers at the University of Pennsylvania and funded by the National Institute of Biomedical Imaging and Bioengineering (NIBIB) have developed a non-invasive brain imaging technique for a class of patients whose epilepsy symptoms do not respond to drug treatment and who would otherwise be poor candidates for seizure-relieving surgeries. Epilepsy affects approximately 65 million people worldwide. Seizure-controlling medications are ineffective in approximately one third of these patients. Alternatively, doctors can perform surgery to remove the source of the seizures, which often is a lesion, or scarring, within the brain. Conventional imaging procedures, such as magnetic resonance imaging (MRI) and positron emission tomography (PET) help surgeons identify and remove brain lesions. Approximately one third of those with drug-resistant epilepsy, however, do not have lesions that conventional brain imaging can detect. Now, researchers report a new specialized imaging technique that can trace the location of seizures that are not detected with conventional MRI or PET. The imaging technique, known as glutamate chemical exchange saturation transfer (GluCEST), was developed in the laboratory of senior author Ravinder Reddy, Ph.D., a professor of radiology and director of the University of Pennsylvania’s Center for Magnetic Resonance and Optical Imaging. The work is reported in the October issue of Science Translational Medicine. “This non-invasive MRI technique images distinct patterns and changes in glutamate levels in brain structures that could be indicative of neurological disorders” explains Richard Conroy, Ph.D., director of the NIBIB Division of Applied Science and Technology. “The research team is pursuing the tracking of glutamate because it is a key amino acid involved in transmitting signals between neurons, making it a potential marker for identifying the region of the brain where abnormal firing of neurons could cause epileptic seizures.” Normally, glutamate acts as an excitatory signal that relays messages through the brain and then quickly dissipates. In previous studies, researchers showed that glutamate does not dissipate in animals and humans with epilepsy, resulting in a build-up of glutamate that causes overstimulation and the onset of seizures. The specialized MRI technique relies on unique chemical properties of glutamate that permit water molecules surrounding the chemical to be visualized at a very high resolution. The increased signal from the surrounding water molecules indicates increased levels of glutamate. The researchers studied how GluCEST imaging detects glutamate in the hippocampus. The hippocampus is a bilateral area of the brain involved in spatial navigation and the conversion of short-term thoughts into long-term memories. Seizures often originate in the temporal lobes of the brain, which include the right and left halves of the hippocampus. In four patients with drug-resistant epilepsy, GluCEST imaging enabled the researchers to detect consistently higher levels of glutamate in the side of the hippocampus where the epileptic seizures originated. The researchers confirmed the results with electroencephalography, which identifies the side of the brain emitting irregular waves as a seizure is occurring. In 11 healthy individuals tested for comparison, the GluCEST signal for glutamate was the equivalent, or normal, in either side of the hippocampus. “The demonstration that GluCEST can localize hot spots of increased glutamate is a promising step towards improved treatment,” says Kathryn Davis, M.D., an assistant professor of neurology at the Perelman School of Medicine at the University of Pennsylvania and lead author of the study. “Finding the epileptic foci in a specific brain region gives clinicians critical information to guide targeted therapies that have the potential to control seizures in patients that currently do not have treatment options.” The researchers are optimistic that the GluCEST imaging technique offers patients the possibility for expanded epilepsy treatments, which could include surgery or laser ablation therapy. Neurostimulation—electrical stimulation similar to therapy for patients with Parkinson’s disease—may also be able to reduce abnormal excitation that produces erratic movements and seizures. The research was supported by the National Institutes of Health through a grant (EB015893) from NIBIB and a grant from the National Institute of Neurological Disorders and Stroke. Additional funding was provided by a McCabe Pilot Award and a University of Pennsylvania Center for Biomedical Image Computing and Analytics Seed Award.
Newswise —  University of Oregon scientists have found that strength in numbers doesn't hold true for microbes in the intestines. A minority population of the right type might hold the key to regulating good health. The discovery, based on research using zebrafish raised completely germ free, is reported in a paper published in the Nov. 11 issue of Cell Host & Microbe. The findings provide a path to study the function of each bacterial species in the gut and to eventually, perhaps, predict and prevent disease, says lead author Annah S. Rolig, a postdoctoral researcher in the UO's Institute of Molecular Biology. In the project, researchers watched for immune response as isolates of species of bacteria, normally associated with healthy zebrafish, were introduced one at a time and in combination into previously germ-free intestines of the fish. In a telling sequence, one bacterial species, Vibrio, drew numerous neutrophils, which indicated a rapid inflammatory response in one fish. Another species, Shewanella, inserted into a separate germ-free fish barely attracted an immune response. In a third germ-free fish, both species were introduced together and assembled with a ratio of 90- percent Vibrio to 10-percent Shewanella. The inflammatory response in the third fish was completely controlled by the low-abundance species. "Until now, we've only been able to capture proportional information, like you'd see displayed in a pie graph, of the makeup of various microbiota, in percentages of their abundance," Rolig said. "Biologists in this field have typically assumed an equal contribution based on that makeup." Low counts of a bacterial species generally have been discounted in importance, but slight shifts in the ratios of abundant microbe populations have been thought to have roles in obesity, diabetes and inflammatory bowel diseases such as Crohn's disease. That thinking is now changing, Rolig said. "The contribution of each bacterium is not equal. There is a per-capita effect that needs to be considered." The keystone - an important participant that functions to regulate a healthy microbiota - may reside in low-abundant bacterial species. The research team found through additional scrutiny that these species secreted molecules - for now unidentified - that allowed them to dampen the immune response to the whole community. "Now we've shown that these minor members can have a major impact. If we can identify these keystone species, and find that in a disease state one species may be missing, we might be able to go in with a specific probiotic to restore healthy functioning," said Rolig, who also is a scientist in the National Institutes of Health-funded Microbial Ecology and Theory of Animals Center for Systems Biology, known as the META Center, at the UO. To develop a model to capture per-capita contributions of microbes in a population, Rolig and her co-authors -- biology graduate student Adam R. Burns, microbiologist Brendan Bohannan of the Institute of Ecology and Evolution and biologist Karen Guillemin, director of the META Center -- turned to UO physicist Raghuveer Parthasarathy. His math-driven model, detailed in the paper, provides formulas that predict collective inflammatory responses of combinations of bacteria. "I'm really proud of this paper because it exemplifies an achievement of one of the major goals of the META Center for Systems Biology, namely to provide a predictive model of how host-microbe systems function," Guillemin said. "This experimental and modeling framework could be readily generalized to more complex systems such as humans, for example to predict disease severity in individuals with inflammatory bowel disease based on the pro-inflammatory capacity of their gut microbes as assayed in cell culture." ### The National Institutes of Health supported the research through grants P50GMO98911 to support the META Center, IF32DK098884 for a postdoctoral fellowship to Rolig and P01HD22486 that supports the UO's zebrafish facility. Sources: Annah S. Rolig, postdoctoral research associate, UO Institute of Molecular Biology, 541-346-5999,, and Karen Guillemin, professor of biology and director of the META Center for Systems Biology, 541-346-5360, Note: The UO is equipped with an on-campus television studio with a point-of-origin Vyvx connection, which provides broadcast-quality video to networks worldwide via fiber optic network. There also is video access to satellite uplink and audio access to an ISDN codec for broadcast-quality radio interviews.
Newswise —  A diet rich in vitamin C could cut risk of cataract progression by a third, suggests a study being published online today in Ophthalmology, the journal of the American Academy of Ophthalmology. The research is also the first to show that diet and lifestyle may play a greater role than genetics in cataract development and severity. Cataracts occur naturally with age and cloud the eye’s lens, turning it opaque. Despite the advent of modern cataract removal surgery, cataracts remain the leading cause of blindness globally.1 Researchers at King’s College London looked at whether certain nutrients from food or supplements could help prevent cataract progression. They also tried to find out how much environmental factors such as diet mattered versus genetics. The team examined data from more than 1,000 pairs of female twins from the United Kingdom. Participants answered a food questionnaire to track the intake of vitamin C and other nutrients, including vitamins A, B, D, E, copper, manganese and zinc. To measure the progression of cataracts, digital imaging was used to check the opacity of their lenses at around age 60. They performed a follow-up measurement on 324 pairs of the twins about 10 years later. During the baseline measurement, diets rich in vitamin C were associated with a 20 percent risk reduction for cataract. After 10 years, researchers found that women who reported consuming more vitamin C-rich foods had a 33 percent risk reduction of cataract progression. Genetic factors accounted for 35 percent of the difference in cataract progression. Environmental factors, such as diet, accounted for 65 percent. These results make the study the first to suggest that genetic factors may be less important in progression of cataract than previously thought.How vitamin C inhibits cataract progression may have to do with its strength as an antioxidant. The fluid inside the eye is normally high in vitamin C, which helps prevents oxidation that clouds the lens. More vitamin C in the diet may increase the amount present in the fluid around the lens, providing extra protection. Researchers noted that the findings only pertain to consuming the nutrient through food and not vitamin supplements. “The most important finding was that vitamin C intake from food seemed to protect against cataract progression,” said study author Christopher Hammond, M.D., FRCOphth, professor of ophthalmology at King’s College London. “While we cannot totally avoid developing cataracts, we may be able to delay their onset and keep them from worsening significantly by eating a diet rich in vitamin C.”
Newswise — Obese young people can still turn their chances of developing life threatening illness around if they change before middle age, says new research. The study looked at the body mass index (BMI) of people when they were young and compared it to when they were middle aged to see whether it affected their risk of heart attack, stroke or diabetes. Men who had high BMI levels at 21, but had lowered their BMI by the time they were 50, had similar or lower rates of diabetes as people who were normal weight when younger, the results showed. In a unique approach, the study used the records of men’s military service, which recorded their BMI at 21, as well as participant recall and followed up with them 30 years later. Lead research Professor Christopher Owen from St George’s University of London said the effects of high BMI early in life may be reversible. “Even in men who carried out UK National Service and were relatively thin in early life compared to more recent men, higher levels of fatness in early adult life appear to be associated with later diabetes,” he said. “However, effects of early body mass appear to be reversible by subsequent weight loss. These findings have important implications for Type 2 diabetes prevention, especially in more recent adults with high levels of obesity.” But the study, which examined almost 5000 men, found that a higher BMI earlier in life did not impact on the risk of heart attack or stroke. However, men who were obese when they were 50 had increased chances of suffering a heart attack, stroke or diabetes. Obesity is the biggest risk factor for type 2 diabetes and over 4 million people in the UK are at high risk of developing the condition.
Newswise —  Resistance and endurance exercises affect the body very differently. These differences suggest that adapting to exercise involves many processes, but scientists have observed that one gene in particular, peroxisome proliferator-activated receptor-gamma coactivator PGC-1α, controls many of them. New research in Physiological Reports shows that although both resistance and endurance exercises activate the PGC-1α gene, the adaptation processes stimulated are not the same and depend on the type of exercise. Proteins run the body: They turn processes on or off or speed them up or slow them down. The body has many different proteins, and the instructions to make them are written on sections of DNA, referred to as genes. Different genes code for different proteins, but different proteins can also come from the same gene. Called isoforms, these proteins are produced when only part of the gene’s code is read. The PGC-1α protein turns on other genes. Several studies have shown that isoforms of PGC-1α exist and that the isoform produced depends on the exercise. In this new study, researchers at the University of Jyväskylä in Finland comprehensively examined the isoforms present shortly after exercising and the genes those isoforms turned on. Samples were taken from the thigh muscles of healthy men after they performed high-intensity resistance exercises or moderate-intensity endurance exercises. The researchers found that both endurance and resistance exercises produced isoforms PGC-1α exon 1b, PGC-1α exon 1b’ and truncated PGC-1α, while only endurance exercise produced PGC-1α exon 1a isoform. Endurance exercise activated genes that stimulated growth of new blood vessels and increased endurance. Resistance exercise also activated a gene that promoted blood vessel growth, along with a gene that encouraged muscle growth. “Our results support that gene expression responses of PGC-1α isoforms may have an important role in exercise-induced muscle adaptations,” the researchers stated. The study “PGC‐1 isoforms and their target genes are expressed differently in human skeletal muscle following resistance and endurance exercise” is published in the October issue of Physiological Reports, a joint journal of the Physiological Society and American Physiological Society.
Newswise — UC Berkeley biologists have discovered the switch that triggers the power kick sperm use to penetrate and fertilize a human egg, uncovering a possible source of male infertility but also a potential target for contraceptives that work in both men and women. The switch is a protein receptor that responds to the female sex hormone progesterone, which is released by the egg or oocyte, the ultimate goal toward which sperm swim. Thousands of these receptors sit on the surface of a sperm’s tail and when the sperm gets close to the egg, the hormone activates the receptor and triggers a cascade of changes that make the tail snap like a whip, powering the sperm into and hopefully through the cells protecting the egg. “If the receptor protein doesn’t recognize progesterone, you would be infertile,” said Melissa Miller, a postdoctoral fellow at both UC Berkeley and UC San Francisco and the first author of a paper reporting the discovery. “This gives us an understanding of another pathway that is involved in human sperm activity.” A drug that inactivates this newly discovered receptor, however, might make a good “unisex” contraceptive – one that could be used by either sexual partner. “What’s really cool is that we have an actual target for unisex contraceptive development,” Miller said. “If you can stop progesterone from inducing a power stroke, sperm are not going to be able to reach or penetrate the oocyte.” While there are other possible targets for a contraceptive that would prevent the initiation of the power stroke, called hyperactivation, or the simultaneous release of enzymes that cut through the protective layer around the egg, “this is one of the better options we have for a unisex contraceptive,” she said. Senior author Polina Lishko, a UC Berkeley assistant professor of molecular and cell biology, noted that many tissues – the brain, the lungs, smooth muscle – contain related progesterone or steroid receptors that may work in a similar manner to trigger major changes in tissues. “Now that we know the players, the next step is to look in other tissues that express these proteins to see whether progesterone acts on them in a similar manner to affect pain threshold adjustment in pain sensing neurons, surfactant production in the lungs or the excessive smooth muscle contractions found in asthma,” she said. “This may be a universal pathway in all cells.” Miller, Lishko and their colleagues will publish their findings in the March 17 “Fast Release” issue of the journalScience. Few known causes of male infertility Today, doctors are unable to determine the cause of nearly 80 percent of all cases of male infertility, in part because little is known about the many molecular steps involved in the production of sperm and its interactions with the egg. Sperm may be to blame in half of all cases of infertile couples. Yet because the U.S. government forbids the use of federal funds for research that brings eggs and sperm together in the same dish, little research has been done on how egg-sperm interactions lead to infertility. And until five years ago, it was very difficult to study the inner workings of sperm – the body’s smallest cell – with ordinary lab techniques. The new discovery comes thanks to techniques that Lishko and her colleague Yuriy Kirichok developed over the past five years at UCSF and UC Berkeley. The techniques allow them to stick electrodes on a sperm’s tail and record its reactions to hormones, key to probing the molecular cascades that govern sperm behavior. That technique led to their discovery that a large receptor on sperm tails – a calcium channel dubbed CatSper – is activated by progesterone from the egg. Progesterone unlocks the channel gate, letting electrically charged calcium atoms flood into the cell. This leads to a biochemical cascade that readies the sperm cell for its last-ditch effort to fertilize the oocyte. Miller and Lishko suspected, however, that progesterone was not acting directly on the calcium channel, but on some other receptor that, in turn, activated the calcium channel. That proved to be the case. They showed that progesterone actually binds to a previously mysterious enzyme called ABHD2, which is found at high levels in sperm. Once progesterone binds to the enzyme, which sits on the surface of the sperm, it removes a lipid (2AG) that has been inhibiting the calcium channel. Released of inhibition, CatSper opens the gate to calcium ions and eventual sperm activation. The inhibitor of the calcium channel CatSper is probably there for a good reason: to prevent sperm from prematurely sprinting toward the egg and using up their limited supply of energy, Miller said. Marathon or team sport? “People tend to think of fertilization as like a marathon, where the fastest, most powerful sperm is going to win,” Miller said. “We think of it like the Tour de France, where the riders in front are blocking the wind for the actual winner. Fertilization is a team sport, where the first sperm clear the way, expending their energy to break through the barrier cells, so that the slow and steady guy can get into the oocyte.” The study also sheds light on a long-standing mystery about steroids like progesterone: why they appear to act in two distinctly different ways. As a sex hormone, progesterone usually triggers a cascade of events in the cell that alter the expression of genes in the nucleus, a process that can take days. But sometimes progesterone causes immediate changes in the cell – something called non-genomic steroid signaling – that evidently use a quicker process than gene expression. Lishko, who studies the sperm of rats, mice, bulls and boars as well as human to understand how fertilization works across different species, says that sperm are a perfect system in which to study non-genomic steroid signaling, since the genes in sperm are silenced and the normal type of steroid signaling is not present. As she and her colleagues uncover the basics of steroid signaling in sperm, the same process can then be studied in many other types of cells, she said. The research was supported by the National Institutes of Health and by Pew Scholars and Alfred P. Sloan Awards to Lishko. Lishko, Miller and Kirichok have filed a patent on usage of ABHD2. Aside from Miller, Lishko and Kirichok, other authors of the paper are Nadja Mannowetz, Anthony Iavarone, Rojin Safavi, Rose Hill and Diana Bautista of UC Berkeley, Elena Gracheva of Yale University and James Smith of UCSF.   Healthy sperm employ a regular sinusoidal tail motion when swimming, unlike the whiplike motion they use when they reach the egg.