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Newswise —  In the U.S., where one of five children entering elementary school is overweight, a healthy diet is critical for preschool children, who are setting their eating patterns for the future. In 2009, more fruits, vegetables, whole grains and low-fat milk were included in the food voucher package provided by USDA’s Special Supplemental Nutrition Program for Women, Infants and Children (WIC). As a result, the diet quality improved for the roughly 4 million children who are served by WIC, according to a study by researchers at UCSF Benioff Children’s Hospital in Oakland, UC San Francisco and UC Agriculture and Natural Resources’ Nutrition Policy Institute. “Although the findings only showed significant improvement for consumption of greens and beans, the other areas for which WIC has put in important efforts – increased consumption of whole fruits rather than fruit juice, increased whole grains – all show trends in the right direction,” said lead author June Tester, a physician at UCSF Benioff Children’s Hospital Oakland, “and there is opportunity for further study in the future when more years have passed after this landmark change in the WIC package.” For the UC study, to be published Thursday, April 7, in the April issue of the journal Pediatrics, researchers analyzed the diets of 1,197 children, ages 2 to 4 years, from low-income households before and after the 2009 change in the food package. The researchers used the National Health and Nutrition Examination Survey (NHANES) to compare a nationally representative sample from 2003 to 2008 with diets in 2011 to 2012. The researchers calculated the Healthy Eating Index (HEI-2010), which is a score with 100 possible points measuring adherence to dietary guidelines, from two recalls by parents of their children’s diets over the previous 24-hour period. For children in households using WIC, this score increased from 52.4 to 58.3 after the policy change. After adjusting for characteristics in the sample and trends in the comparison group, the researchers showed that there was an increase of 3.7 points that was attributable to the WIC package change. This represents important evidence of an improvement in the diets for these children in WIC households. “Vegetables are part of a healthful diet, but in general, children don’t eat enough of them,” Tester said. Using the Healthy Eating Index, the researchers calculated the Greens and Beans score, which counts dark green vegetables and includes any legumes, such as beans and peas, that were not already counted as protein foods on a different score. After the food package was changed, the Greens and Beans score increased for children in WIC but not for their counterparts. Roughly half of the children in WIC households had eaten some vegetables, whereas only one in five non-WIC children had consumed any green vegetables at all in the two days their parents were surveyed. The change in the WIC food package is an important policy change in the effort to improve the quality of diets of young children, said Tester, a pediatrician. Tester noted that the results of this study will be useful to the Institute of Medicine committee that is reviewing and assessing the nutritional status and food needs of the WIC-eligible population and the impact of the 2009 revision to WIC food packages. The committee will make recommendations for changing the food packages. “Increasing consumption of nutritious foods such as green leafy vegetables and whole grains in the low-income children served by WIC will help them establish healthier eating patterns for their future,” said co-author Patricia Crawford, UC Cooperative Extension nutrition specialist with UC ANR’s Nutrition Policy Institute. The switch from whole milk to low-fat milk was well received by the clientele and did not result in decreased milk consumption among the preschoolers, noted Tester, Crawford and co-author Cindy Leung, postdoctoral scholar at UCSF Center for Health and Community. This study is the first to report on the significant improvements in diet quality in young children associated with the WIC package change using a nationally representative sample, and the first to do so with the updated Healthy Eating Index (HEI-2010). The National Institutes for Health funded this study.

Newswise —  There may be a hidden cost to the old adage of pulling oneself up by the bootstraps: Research out of the University of Georgia suggests the unintended stress spurred by upward mobility can pose an unintended health risk later down the road. Previous studies have shown the negative health effect that stress can cause, particularly on people coming from lower socioeconomic backgrounds. But this study specified the approach and narrowed it down to just look at the effect on “future oriented” adolescents who strive to break the cycle and earn higher levels of education and income. Researchers in the UGA College of Family and Consumer Sciences, including professor K.A.S. Wickrama, assistant research scientist Catherine O’Neal and graduate student Tae Kyoung Lee, combed through a 13-year national study that contained clinical health data from over 11,000 participants as they aged into adulthood. They found that young adults who come from adverse backgrounds—but also show resilience to break that pattern and achieve a higher social status—are more likely to be unhealthy later in life than those not motivated to change their circumstances. Specifically, the researchers found that stress increased participants’ risk of developing cardio-metabolic diseases, like diabetes, heart disease and stroke. The study, published in the Journal of Youth and Adolescence, relied on self-reported stress from participants to determine the cause and clinical markers including blood pressure, body mass index, glucose levels and others to determine subsequent health effects. As young adults work to break the cycle of poverty or strive toward being the first in their family to go to college, they experience a disproportionate burden of stress—and were not resilient in terms of their future health due to the combined burden of lived adversity and striving to change it. This stress is then likely to cause irreversible weathering in their body systems. “The act of striving for socioeconomic attainment is itself stressful for youth already experiencing stressful life events,” said Wickrama, the Athletic Association Professor in Human Development and Family Science. The findings suggest that although there may be long-term health benefits associated with increased socioeconomic status, there may also be consequences due to the subsequent mental and physical strain. The notion seems counterintuitive at first, but the relationship between stress and health risks has been shown before. This study shows the intensification of health effects for future-oriented youth with a stressful family background. Researchers said that the study shows the need for institutional policy that supports young people who show signs of future upward orientation and come from disadvantaged backgrounds. “In order to reduce health vulnerability and the burden that comes as a cost of succeeding,” said O’Neal, at-risk youth “need support through preventative measures.”

Newswise —  A research team led by University of Arkansas chemist Jingyi Chen and University of Arkansas for Medical Sciences microbiologist Mark Smeltzer has developed an alternative therapeutic approach to fighting antibiotic-resistant infections. The novel method uses a targeted, light-activated nanodrug consisting of antibiotic-loaded nanoconstructs, which are nanoscale cages made of gold and coated with polydopamine. The antibiotic is loaded into the polydopamine coating. The gold nanocages convert laser irradiation to heat, resulting in the photothermal effect and simultaneously releasing the antibiotic from the polydopamine coating. “We believe that this approach could facilitate the effective treatment of infections caused by antibiotic-resistant bacteria, including those associated with bacterial biofilms, which are involved in a wide variety of bacterial infections,” said Chen, assistant professor in the Department of Chemistry and Biochemistry in the J. William Fulbright College of Arts and Sciences. Microbial resistance to antibiotics has become a growing public health concern in hospitals and the community at large, so much so that the Infectious Diseases Society of America has designated six bacterial species as “ESKAPE pathogens” – Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter species. This designation reflects the limited availability of antibiotics that can be used to treat infections caused by these species. “It is also estimated that 80 percent of all bacterial infections involve formation of a biofilm, and all of these infections share the common characteristic of intrinsic resistance to conventional antibiotic therapy,” said Smeltzer, professor in the Department of Microbiology and Immunology at UAMS and director of the Center for Microbial Pathogenesis and Host Inflammatory Responses. “Intrinsic resistance refers to the fact that bacteria within a biofilm exhibit a therapeutically relevant level of resistance to essentially all antibiotics." Researchers in Smeltzer’s laboratory study the ESKAPE pathogen Staphylococcus aureus. They focus on how the pathogen causes biofilm-associated bone infection and infections associated with orthopaedic implants. But, as Smeltzer explains, there are many other examples in infections – intravenous catheters and vascular grafts, for example – caused by Staphylococcus aureus. The team used Staphylococcus aureus as the proof-of-principle pathogen to demonstrate the potency of their nanodrug. The combination of achieving a photothermal effect and controlled release of antibiotics directly at the site of infection was achieved by laser irradiation at levels within the current safety standard for use in humans. The therapeutic effects of this approach were validated using planktonic bacterial cultures – bacterial cells that are free-floating rather than contained with a biofilm – of both methicillin-sensitive and methicillin-resistant Staphylococcus aureus strains. However, the method was subsequently shown to be effective even in the context of an intrinsically resistant biofilm. “The even better news is that the technology we developed would be readily adaptable to other bacterial pathogens that cause such infections, including the other ESKAPE pathogens,” Smeltzer said. The researchers’ work was recently published in ACS Infectious Diseases, a publication of the American Chemical Society (ACS) and “the first journal to highlight chemistry and its role in the multidisciplinary and collaborative field of infectious disease research.”

Newswise — A single dose of oxytocin nasal spray, known to reduce food intake, decreases impulsive behavior in overweight and obese men, according to a preliminary study to be presented Saturday at the Endocrine Society’s 98th annual meeting in Boston. Oxytocin nasal spray (made by Novartis) is a synthetic version of the hormone oxytocin, which is important for controlling food intake and weight. It is approved in Europe but not in the United States other than in clinical trials. Oxytocin is available in the United States as an intravenous or injectable drug (Pitocin) to induce labor. Researchers from Massachusetts General Hospital reported last year that oxytocin nasal spray reduced intake of calories and fat at a test meal without affecting appetite, but they were not sure how the drug has that affect. Results of their new pilot study in 10 overweight and obese men suggest that one way oxytocin lowers food intake might be by improving self-control, said co-investigator Franziska Plessow, PhD, an instructor in medicine at Harvard Medical School and a research fellow in the Neuroendocrine Unit at Massachusetts General Hospital, Boston. “Knowing the mechanisms of action of intranasal oxytocin is important to investigating oxytocin as a novel treatment strategy for obesity,” Plessow said. “This information may allow us to move forward to large clinical trials, identify who can benefit from the drug, and help optimize the treatment.” To demonstrate the study subjects’ ability to suppress impulsive behavior, the investigators administered a psychology research test called the stop-signal task. In this test, the subject sat in front of a computer and became trained to respond to a square symbol on the computer screen by pressing a designated left button on the keyboard and to a triangle by pressing a right button. After the subject became familiar with that task, he was told to not press a button when he saw a symbol but heard a beep (the stop signal). Because the beep occurred after the symbols appeared with a varying delay that was adjusted to each subject, the new task required the subject to control the behavioral impulse to respond, Plessow explained. Participants took the test on two occasions 15 minutes after they self-administered a dose of nasal spray in each nostril. In a randomly assigned order, one day they received oxytocin and another they received a placebo, or dummy drug. Neither participants nor the tester knew which treatment they received. The men ranged in age from 23 to 43 years and were overweight or obese (BMI ranging from 27.7-33.9 kg/m2). The study, which received pilot grants from the National Institutes of Health-funded Boston Nutrition Obesity Research Center and Nutrition Obesity Research Center at Harvard, had exciting results, according to Plessow. After receiving oxytocin, participants less frequently pressed the button when they were not supposed to. This demonstrated that they were acting less impulsively and exerting more control over their behavior after receiving oxytocin, she said. Plessow said more study is necessary to determine how oxytocin alters self-control and how important this mechanism is in regulating food intake since not all overeating relates to poor self-control. They also will need to test the drug in women. “Our preliminary results in men are promising,” she said. “Oxytocin nasal spray showed no strong side effects and is not as invasive as obesity surgery.” Endocrinologists are at the core of solving the most pressing health problems of our time, from diabetes and obesity to infertility, bone health, and hormone-related cancers. The Endocrine Society is the world’s oldest and largest organization of scientists devoted to hormone research and physicians who care for people with hormone-related conditions.

Newswise — Consumption of fructose, a fruit-derived sugar present in many sweetened beverages and processed foods, has been associated with epidemic levels of diabetes, obesity, metabolic syndrome and hypertension in the U.S. and around the world. New research presented today at the Experimental Biology 2016 meeting in San Diego further supports this link, finding that high levels of fructose similar to amounts consumed within the American diet may predispose individuals to fast-onset, salt-sensitive hypertension. “A majority of American adults consume 10 percent or more of total calories from added sugars with a subset taking in more than 25 percent of total calories from added sugars,” said lead author Kevin Gordish, PhD. Because beverages are the most common source of added sugars in the American diet, the research team gave rats drinking water with 20 percent fructose—to simulate excessive human soft-drink consumption—and compared them with rats who received plain water in addition to their food for two weeks. During the second week, the rats receiving 20 percent fructose were also given additional salt in their diets. “The specific combination of fructose and high salt introduced in the second week rapidly increased blood pressure, resulting in hypertension. Fructose-linked hypertension was associated with increased sodium retention, decreased sodium excretion and diminished factors that help rid the body of excess salt. This observation of fructose-linked hypertension was only seen a diet with fructose and high salt and not a normal salt diet,” Gordish said. “Fructose intake, similar to amounts consumed within the American diet, predisposed normal rats to a rapid onset of salt-sensitive hypertension. Fructose-linked hypertension was unambiguously due to fructose (and not glucose). Further, fructose had distinct deleterious effects in the kidney not seen with the same amount of glucose.” The results have implications for the U.S. in general and certain ethnic groups such as African Americans, who have a high rate of incidence of salt-sensitive hypertension, in particular. Overall, these findings raise concern about the amount of fructose and salt found in the American diet.

Newswise — A simple blood test can rapidly and accurately detect mutations in two key genes in non-small cell lung tumors, researchers at Dana-Farber Cancer Institute and other institutions report in a new study – demonstrating the test’s potential as a clinical tool for identifying patients who can benefit from drugs targeting those mutations. The test, known as a liquid biopsy, proved so reliable in the study that the Dana-Farber/Brigham and Women’s Cancer Center (DF/BWCC) this week became the first medical facility in the country to offer it to all patients with non-small cell lung cancer (NSCLC), either at the time of first diagnosis or of relapse following previous treatment. NSCLC is the most common form of lung cancer, diagnosed in more than 200,000 people in the United States each year, according to the American Cancer Society. An estimated 30 percent of NSCLC patients have mutations in either of the genes included in the study, and can often be treated with targeted therapies. The study is being published online today by the journal JAMA Oncology. The liquid biopsy tested in the study – technically known as rapid plasma genotyping – involves taking a test tube-full of blood, which contains free-floating DNA from cancer cells, and analyzing that DNA for mutations or other abnormalities. (When tumor cells die, their DNA spills into the bloodstream, where it’s known as cell-free DNA.) The technique, which provides a “snapshot” of key genetic irregularities in a tumor, is a common tool in research for probing the molecular make-up of different kinds of cancers. “We see plasma genotyping as having enormous potential as a clinical test, or assay – a rapid, noninvasive way of screening a cancer for common genetic fingerprints, while avoiding the challenges of traditional invasive biopsies,” said the senior author of the study, Geoffrey Oxnard, MD, thoracic oncologist and lung cancer researcher at Dana-Farber and Brigham and Women’s Hospital. “Our study was the first to demonstrate prospectively that a liquid biopsy technique can be a practical tool for making treatment decisions in cancer patients. The trial was such a success that we are transitioning the assay into a clinical test for lung cancer patients at DF/BWCC.” The study involved 180 patients with NSCLC, 120 of whom were newly diagnosed, and 60 of whom had become resistant to a previous treatment, allowing the disease to recur. Participants’ cell-free DNA was tested for mutations in the EGFR and KRAS genes, and for a separate mutation in EGFR that allows tumor cells to become resistant to front-line targeted drugs. The test was performed with a technique known as droplet digital polymerase chain reaction (ddPCR), which counts the individual letters of the genetic code in cell-free DNA to determine if specific mutations are present. Each participant also underwent a conventional tissue biopsy to test for the same mutations. The results of the liquid biopsies were then compared to those of the tissue biopsies. The data showed that liquid biopsies returned results much more quickly. The median turnaround time for liquid biopsies was three days, compared to 12 days for tissue biopsies in newly diagnosed patients and 27 days in drug-resistant patients. Liquid biopsy was also found to be highly accurate. In newly diagnosed patients, the “predictive value” of plasma ddPCR was 100 percent for the primary EGFR mutation and the KRAS mutation – meaning that a patient who tested positive for either mutation was certain to have that mutation in his or her tumor. For patients with the EGFR resistance mutation, the predictive value of the ddPCR test was 79 percent, suggesting the blood test was able to find additional cases with the mutation that were missed using standard biopsies. “In some patients with the EGFR resistance mutation, ddPCR detected mutations missed by standard tissue biopsy,” Oxnard remarked. “A resistant tumor is inherently made up of multiple subsets of cells, some of which carry different patterns of genetic mutations. A single biopsy is only analyzing a single part of the tumor, and may miss a mutation present elsewhere in the body. A liquid biopsy, in contrast, may better reflect the distribution of mutations in the tumor as a whole.” When ddPCR failed to detect these mutations, the cause was less clear-cut, Oxnard says. It could indicate that the tumor cells don’t carry the mutations or, alternatively, that the tumor isn’t shedding its DNA into the bloodstream. This discrepancy between the test results and the presence of mutations was less common in patients whose cancer had metastasized to multiple sites in the body, researchers found. The ddPCR-based test, or assay, was piloted and optimized for patients at the Translational Resarch lab of the Belfer Center for Applied Cancer Science at Dana-Farber. It was then validated for clinical use at Dana-Farber’s Lowe Center for Thoracic Oncology. An advantage of this form of liquid biopsy is that it can help doctors quickly determine whether a patient is responding to therapy. Fifty participants in the study had repeat testing done after starting treatment for their cancer. “Those whose blood tests showed a disappearance of the mutations within two weeks were more likely to stay on the treatment than patients who didn’t see such a reduction,” said the study’s lead author, Adrian Sacher, MD, of Dana-Farber and Brigham and Women’s Hospital. And because tumors are constantly evolving and acquiring additional mutations, repeated liquid biopsies can provide early detection of a new mutation – such as the EGFR resistance mutation – that can potentially be treated with targeted agents. “The study data are compelling,” said DF/BWCC pathologist Lynette Sholl, MD, explaining the center’s decision to begin offering ddPCR-based liquid biopsy to all lung cancer patients. “We validated the authors’ findings by cross-comparing results from liquid and tissue biopsies in 34 NSCLC patients. To work as a real-world clinical test, liquid biopsy needs to provide reliable, accurate data and be logistically practical. That’s what we’ve seen with the ddPCR-based blood test. “The test has great utility both for patients newly diagnosed with NSCLC and for those with a recurrence of the disease,” she continued. “It’s fast, it’s quantitative (it indicates the amount of mutant DNA in a sample), and it can be readily employed at a cancer treatment center.” The co-authors of the study are Cloud Paweletz, PhD, Allison O’Connell, BSc, and Nora Feeney, BSc, of the Belfer Center for Applied Cancer Science at Dana-Farber; Ryan S. Alden BSc, and Stacy L. Mach BA, of Dana-Farber; Suzanne E. Dahlberg, PhD, of Dana-Farber and Harvard T.H. Chan School of Public Health; and Pasi A. Jänne, MD, PhD, of Dana-Farber, the Belfer Center, and Brigham and Women’s Hospital.

Newswise — For most people, the culmination of a good life is a “good death,” though what that means exactly is a matter of considerable consternation. Researchers at the University of California, San Diego School of Medicine surveyed published, English-language, peer-reviewed reports of qualitative and quantitative studies defining a “good death,” ultimately identifying 11 core themes associated with dying well. The findings are published in the April 2016 issue of the American Journal of Geriatric Psychiatry. The research team, headed by senior author Dilip Jeste, MD, Distinguished Professor of Psychiatry and Neurosciences and director of the Sam and Rose Stein Institute for Research on Aging at UC San Diego School of Medicine, focused on three groups of stakeholders: patients, family members (before or during bereavement) and health care providers. “This is the first time that data from all of the involved parties have been put together,” said Jeste, who is also associate dean for healthy aging and senior care at UC San Diego School of Medicine. “Death is obviously a controversial topic. People don’t like to talk about it in detail, but we should. It’s important to speak honestly and transparently about what kind of death each of us would prefer.” The literature search culled through 32 qualifying studies. It identified 11 core themes of good death: preferences for a specific dying process, pain-free status, religiosity/spirituality, emotional well-being, life completion, treatment preferences, dignity, family, quality of life, relationship with the health care provider and “other.” The top three themes across all stakeholder groups were preferences for specific dying process, pain-free status and emotional well-being. For other themes, however, different stakeholders put somewhat different levels of emphasis. For example, patients more often cited religiosity/spirituality as important than did family members, who believed dignity and life completion were more critical to a good death. Health care providers tended to represent a middle ground between patients and family members. “Clinically, we often see a difference between what patients, family members and health care providers value as most important near the end of life”, said first author Emily Meier, PhD, a psychologist at Moores Cancer Center at UC San Diego Health. “Ultimately, existential and other psychosocial concerns may be prevalent among patients, and this serves as a reminder that we must ask about all facets of care that are essential at the end of life.” The bottom line, said Jeste, is “ask the patient.” “Usually, patients know what they want or need and there is relief in talking about it. It gives them a sense of control. I hope these findings spur greater conversation across the spectrum. It may be possible to develop formal rating scales and protocols that will prompt greater discussion and better outcomes. You can make it possible to have a good death by talking about it sometime before.”

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 — 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.