Culture

Our lungs, bones, blood vessels and other major organs are made up of cells, and one way our bodies keep us healthy is by using protein messengers known as ligands that bind to receptors on the surfaces of cells to regulate our biological processes. When those messages get garbled, it can make us ill with a host of different diseases.

Now a team led by Stanford bioengineer and department chair Jennifer Cochran has tweaked one ligand in slightly different ways to produce two startlingly different results. One set of alterations caused neuronal cells to regenerate, while different tweaks to the same protein inhibited lung tumor growth.

The experiments her team described in the Proceedings of the National Academy of Sciences were performed on rat and human cells or in mice that model actual diseases and are still far from being tested in humans. But the results show how scientists are becoming increasingly adept at tinkering with the body's protein-based control mechanisms to help vital organs heal themselves.

"These proteins can hopefully one day be used to treat neurodegenerative disease, as well as cancers and other disorders such as osteoporosis and atherosclerosis," Cochran said.

Her lab studies how ligands and receptors work together to deliver messages to cells, and how these interactions can be engineered to create potent therapeutic agents. Shape is the critical concept. Like all proteins, ligands and receptors are made up of many different amino acids strung together like pearls and folded into distinct three-dimensional shapes. A ligand with the right shape fits its matching receptor like a key fits a lock.

By using sophisticated molecular engineering techniques, the researchers can change the lineup of amino acids in a ligand, essentially making millions of keys that they then screen to see which might unlock its matching receptor in some desirable way. A key that fits better and trips the lock more efficiently -scientists call this a superagonist -- might transmit messages instructing cells to grow more robustly. Bioengineering can also be used to turn ligands into antagonists - keys that also fit the receptor lock, but in a way that blocks the signal and thus might retard a function like cell growth.

Last year, Cochran collaborated with UC San Francisco cancer researcher Alejandro Sweet-Cordero to publish a paper showing how an engineered version of the receptor protein CNTFR, helped stop lung tumor growth in rodents.

The new experiments build on that work as a research team led by graduate student Jun Kim engineered the ligand known as CLCF1 which binds with the CNTFR receptor. By making one set of amino acid alterations in CLCF1, Kim turned that ligand into a superagonist. When they added this superagonist to a tissue culture of injured neuronal cells, the engineered CLCF1 increased the messaging signals that promote the growth of axons, the fibers that transmit nerve impulses, suggesting that this modified ligand was encouraging wounded neurons to regenerate themselves.

Conversely, Kim and his fellow researchers showed that, by introducing a few additional amino acid alterations to CLCF1, they could turn this ligand into a potent antagonist that could inhibit the growth of lung tumors in mice, suggesting a different possible medicinal use for this variant of the molecule.

Cochran has spent her career developing novel engineered proteins as therapeutic candidates for oncology and regenerative medicine applications. Several of the molecules discovered in her lab have moved forward into early through late stage pre-clinical development, with her most advanced therapeutic, a treatment for ovarian and kidney cancer, now in human trials. She is optimistic that engineered ligands and receptors will continue to prove to be a promising class of drugs to fight illness and maintain health.

"I have long been fascinated with how proteins function as nature's molecular machines, and how the tools of engineering allow us to shape protein structure and function with the creativity of an artist, in this case using amino acids as our palette."

Tanycytes are cells in the brain that tell the brain about the food we have eaten

When they are stimulated by light researchers from the University of Warwick found that appetite increases

Researchers have concluded that tanycytes are glial cells, and deliver signals to neurons in the brain to activate appetite

Tanycytes are glial cells, which communicate with neurons in the brain to inform it of what we have eaten. Researchers from the School of Life Sciences at the University of Warwick have found when tanycytes are selectively stimulated appetite was increased.

It has previously been discovered that tanycytes - cells found in part of the brain that controls energy levels - detect nutrients in food and tell the brain directly about the food we have eaten.

Tanycytes do this by responding to amino acids found in foods, via the same receptors that sense the flavour of amino acids ("umami" taste), which are found in the taste buds of the tongue.

In the paper 'Hypothalamic tanycytes generate acute hyperphagia through activation of the arcuate neuronal network.' published today, the 8th June, in the journal PNAS, researchers from the School of Life Sciences at the University of Warwick, explain how tanycytes can increase appetite.

Tanycytes are glial cells located in the centre of the brain where they line one of the fluid filled spaces known as ventricles. They are able to senses or "taste" the nutrients in the cerebrospinal fluid within the ventricle. The amount of nutrients in this fluid varies depending how much has been eaten. A key question has been whether the tanycytes can relay this information about nutrients to the nearby neurons that regulate appetite and how much energy that is expended via activity or the generation of body heat.

By getting tanycytes to selectively express a light sensitive ion channel, researchers were able to very activate them very specifically and show that this causes nearby neurons to become active. By looking at the identity of the activated neurons the researchers found that the tanycytes could turn on two different pathways involved in the control of feeding.

One pathway is associated with an increased drive to feed, whereas the other pathway is associated a reduced drive to feed and greater energy expenditure. From this it would not be clear which of these two opposed pathways "wins".

By studying how stimulation of tanycytes changes feeding behaviour, the researchers showed that it resulted in a short-term increase in food intake: i.e. the drive to feed more overcame the opposing drive to feed less and expend more energy.

Professor Nicholas Dale, from the School of Life Sciences at the University of Warwick explains:

"Tanycytes respond to nutrients that signal the effect of feeling full, so we'd expect that when tanycytes are stimulated you would eat less, but surprisingly we found that you actually eat more. We have established a link between tanycytes and food intake, but we still don't completely understand how they will contribute to the control of body weight in the longer term."

Dr Matei Bolborea, the first author of the study stated:

"Neuronal mechanisms controlling appetite have been studied for decades. Our discovery has added an unexpected new player into this neural circuit. Our important finding is that tanycytes have an active role in increasing appetite. In the future, these cells could become potential targets to reduce or increase food intake for therapeutic purposes."

Replacing Gross Domestic Product (GDP) with a new "ecosystem" measure reveals the enormous value of the natural world, new research shows.

GDP - widely used by decision-makers around the world - summarises the value of all goods and services bought and sold in a country during a specific period as a single figure.

But it takes no account of how nature contributes to economic activity and human wellbeing.

The new study, by an international team including the University of Exeter, calls this a "critical omission" and suggests a new way to measure that missing value of nature: "Gross Ecosystem Product" (GEP).

This new approach is demonstrated in action through a case study in China, where the government is working to develop and implement GEP as a comparable compliment to GDP.

“To achieve sustainable development, we need to move beyond conventional economic measures like GDP,” said Professor Ian Bateman, of the Department of Economics at the University of Exeter Business School, the Land, Environment, Economics and Policy Institute (LEEP) and the Global Systems Institute.

"The global economy, as conventionally measured by GDP, more than doubled between 1990 and 2015.

"However, at the same time our stocks of 'ecosystem assets' - such as forests, grasslands, wetlands, fertile soils and biodiversity - have come under increasing pressure.

"These things are obviously valuable in many ways - including to human wellbeing. However, in this study we examine the benefits they bring us measured in a way that governments and business can understand.

"GEP can provide decision-makers with clear and compelling evidence of the value of the natural world expressed using money."

The study focusses on China's Qinghai province, which contains the sources of the Mekong, Yangtze and Yellow Rivers.

It concludes that GEP was actually greater than GDP in the year 2000. Even after the rapid growth of the region's economy in the first decade and a half of this century, GEP was still about three quarters the size of GDP by 2015.

Unsurprisingly, about two thirds of Qinghai's GEP was found to come from water-related "ecosystem services" (benefits to humans from the natural world).

"We have shown that GEP can be calculated in a clear and transparent manner, similar to that used for GDP," said Professor Bateman.

"China is already using GEP in decision-making in multiple ways, which is a step in the right direction.

"GEP could be used across China and around the world, to guide investments in ecosystem conservation and restoration.

"By setting out the data and methods in a clear and transparent manner, we hope to provide a useful template to account for the value of nature in countries worldwide - one that can be improved through time as data and methods improve."

Ecosystem services can be classified into material services (the contribution of nature to the provision of food, water supply, etc), regulating services (the contribution of nature to carbon sequestration, flood mitigation, soil retention, sandstorm prevention, etc) and non-material services (the contribution of nature to ecotourism, nature experience for mental health, etc).

This study is one of the first outputs of an ongoing collaboration between LEEP and leading academics in the USA, including the NatCap centre based at Stanford University, and China, including the Chinese Academy of Sciences.

To have a more sustainable world, people need to put a dollar value on nature's contributions.

In this week's interdisciplinary journal - Proceedings of the National Academy of Sciences, an international group of scholars show that gross domestic product (GDP) fails to fully capture nature's contributions to economic activity and human well-being. In addition to the D - domestic, there needs to be an E for ecosystem. Gross ecosystem product (GEP) summarizes the economic value of nature's contributions to humans.

Valuing nature's contribution globally is a critical step to affording the world's forests, grasslands, fertile soils, wetlands and biodiversity the protections and respect given to traditional economic powerhouses.

"We must bring ecosystem services to the business table for a sustainable future," said Jianguo "Jack" Liu, director of Michigan State University's Center for Systems Integration and Sustainability. "The world is losing a tremendous amount of its natural capital - clean water, biodiversity, sequestering greenhouse gases. It's time we give people a way to understand what they stand to lose economically."

Both GEP and GDP use accounting measures to estimate the economic value of goods and services. The group assigned GEP to western China's Qinghai Province, which is known as the water tower of east and southeast Asia as it is the source of three major rivers. Qinghai also is a biodiversity hotspot that has suffered from population increases and overgrazing.

By applying new accounting to Qinghai's natural capital, the group was able to not only put Qinghai's ecosystems on a balance sheet, but also show only a third of the economic value generated in the province's ecosystems was provided to its residents. The rest were exported to other provinces of China and other countries of the world. This demonstrates the importance of human-nature interactions not only within a place but also across adjacent and distant places on this metacoupled planet.

Color awareness has long been a puzzle for researchers in neuroscience and psychology, who debate over how much color observers really perceive. A study from Dartmouth in collaboration with Amherst College finds that people are aware of surprisingly limited color in their peripheral vision; much of our sense of a colorful visual world is likely constructed by our brain. The findings are published in the Proceedings of the National Academy of Sciences .

To test people's visual awareness of color during naturalistic viewing, the researchers used head-mounted virtual reality displays installed with eye-trackers to immerse participants in a 360-degree real-world environment. The virtual environments included tours of historic sites, a street dance performance, a symphony rehearsal and more, where observers could explore their surroundings simply by turning their heads. With the eye-tracking tool, researchers knew exactly where an observer was looking at all times in the scene and could make systematic changes to the visual environment so that only the areas where the person was looking were in color. The rest of the scene in the periphery was desaturated so that it had no color and was just in black and white. After a series of trials, observers were asked a series of questions to gauge if they noticed the lack of color in their periphery. A supplemental video from the study illustrates how the peripheral color was removed from various scenes.

In your visual field, your periphery extends approximately 210 degrees, which is similar to if your arms are stretched out on your left and right. The study's results showed that most people's color awareness is limited to a small area around the dead center of their visual field. When the researchers removed most color in the periphery, most people did not notice. In the most extreme case, almost a third of observers did not notice when less than five percent of the entire visual field was presented in color (radius of 10 degrees visual angle).

Participants were astonished to find out later that they hadn't noticed the desaturated periphery, after they were shown the changes that were made to a virtual scene that they had just explored.

A second study tasked the participants to identify when color was desaturated in the periphery. The results were similar in that most people failed to notice when the peripheral color had been removed. A large number of people participated in the two studies, which featured nearly 180 participants in total.

"We were amazed by how oblivious participants were when color was removed from up to 95 percent of their visual world," said senior author, Caroline Robertson, an assistant professor of psychological and brain sciences at Dartmouth. "Our results show that our intuitive sense of a rich, colorful visual world is largely incorrect. Our brain is likely filling-in much of our perceptual experience."

Previous studies evaluating the limitations of visual awareness often relied on participants staring at video content on computer screens directly in front of them. By leveraging the virtual reality experience, this research approach is novel, as the 360-degree environment is more similar to the way people experience the real-world.

Hollings Cancer Center researcher Chanita Hughes-Halbert, Ph.D., said this is illustrated in two recent health disparity studies, both reported online in April in the medical journal Ethnicity and Disease. These two studies are a part of work being done by the Transdisciplinary Collaborative Center in Precision Medicine and Minority Men's Health at the Medical University of South Carolina.

The two studies conclude that it is important to have effective strategies for chronic disease prevention and management for male minority prostate cancer patients as well as male veterans who have experienced various health issues.

The studies were initially funded in August 2016 through an $8 million, 5-year grant from the National Institute of Minority Health and Health Disparities (NIMHD). The grant helped to establish the Transdisciplinary Collaborative Center in Precision Medicine and Minority Men's Health at MUSC that is led by Hughes-Halbert.

The focus of the studies is on the health of minority men and also precision medicine -- in which doctors select treatments that are most likely to help patients based on a genetic understanding of their diseases. This is an area of expertise for Hughes-Halbert, who is part of the Hollings Cancer Control Program at MUSC.

COVID-19 has brought health disparities into the spotlight, which is shedding more light on the topic, a trend she is glad to see, she said. Data from the Centers for Disease and Control and Prevention (CDC) shows that COVID-19 disproportionately affects African American communities. Though research is currently underway on this issue, a recent study showed that counties across the nation that are predominantly black account for over half of coronavirus cases in the U.S. and nearly 60% of deaths.

"COVID-19 is showing all of the ways in which racial and ethnic minorities and individuals from other medically underserved groups are disadvantaged," Hughes-Halbert said. "In addition to having health-related risk factors for COVID-19, racial minorities are likely to be particularly vulnerable to the adverse economic impact of COVID-19."

Researchers believe the COVID-19 health disparities stem from underlying health conditions that affect more African Americans, such as high blood pressure and diabetes. Her studies also suggest the importance of looking into underlying chronic conditions in minority populations.

Hughes-Halbert's studies showed that better chronic disease management is needed among prostate cancer survivors, and training programs are needed to help veterans recover from health issues based on social determinants, such as marital and economic status.

She said health disparities can stem from multiple factors, including poverty; exposure to environmental hazards, such as heavy pollution; inadequate access to health care; individual and behavioral factors; and educational inequalities.

"The key points from these two studies are that it's essentially important that there be effective strategies for chronic disease management, and it can't be neglected," Hughes-Halbert said.

Patients with Chronic Diseases

In the prostate cancer study reported online in Ethnicity & Disease, Hughes-Halbert examined the rates of comorbidity, which refers to the presence of two chronic diseases or conditions in a patient. The research investigated how the health of prostate cancer patients was managed. These patients were each treated with a radical prostatectomy, the surgical removal of all or part of the prostate gland.

The researchers examined the association between patients who had two chronic diseases (comorbidity status) and their race; clinical factors, such as high blood pressure; and health behaviors, such as patients who exercised regularly and ate a balanced diet, for cancer control. Nearly half of the men in the study who were either short-term or long-term prostate cancer survivors had at least one other chronic disease that was not effectively managed.

The study showed that 51% of participants had an underlying health issue, with high blood pressure being the most common.

Diseases such as hypertension, heart disease and diabetes tend to be more prevalent among African Americans. Interestingly, the findings from this particular study suggested that a prostate cancer survivor's race did not contribute to their health issues. Rather, it may be more related to geographic disparities.

South Carolina is a rural state where some patients do not have access to health care near their homes. All 46 counties in the state have rural populations.

Based on the study's results, Hughes-Halbert plans to extend her research to look at the nature of distribution of chronic diseases based on certain groups of people who have restricted access to social resources, also known as social deprivation. Her team also will focus on developing clinical strategies to improve the chronic disease management of cancer survivors. Strategies will not only be explored at a health care system level but also an individual level to promote more effective disease management through diet and physical activity.

Along with Hughes-Halbert, research group members include Melanie Jefferson, Ph.D., Richard R. Drake, Ph.D., Michael Lilly, M.D., and Sarah Tucker Price, M.D., Ph.D.

Patient Recovery Research

Hughes-Halbert's study involving veterans examined the relationships between resiliency, sociodemographic factors and allostatic load among male veterans. Resiliency is whether a patient is able to recover quickly from experiencing health difficulties. Allostatic load is the stress and strain on the body.

Results of the study concluded that 60% of participants reported they were able to adapt, and 40% reported they were able to recuperate after their health difficulties.

Patients with a higher income and lower prostate-specific antigen (PSA) level, a protein produced by normal and malignant cells of the prostate gland, were significantly correlated with greater odds of adjusting to their health difficulties and recovering.

Interestingly, veterans who were minorities (nonwhite males) in the study were more likely than nonminority men to report that they were able to recover from their health issues, showing that minority men were not at a disadvantage. Married men were also significantly more likely than unmarried men to report that they were able to "bounce back" from their health issues. These results prove that health disparities do not always equate to race or ethnicity. Disparities can affect various groups of people.

"The data allowed us to question if the results were because we live in a state that has health care professional shortage areas and other issues that make accessing quality health care for chronic disease management and prevention more difficult, regardless of racial or ethnic background," Hughes-Halbert said.

Hughes-Halbert plans to do a follow-up study to understand and explore helpful ways that allow patients to recover from their health issues.

While most men reported during the study that they were able to adapt when changes in health occurred, researchers believe additional support may be helpful to enhance a patient's ability to recover from injury, illness or hardship. It may be important to target these programs to veterans, based on their social conditions of health such as education, income and racial/ethnic background.

This study's research team includes Jefferson, Linda Ambrose, R.N., Susan Caulder, R.N., and Stephen J. Savage, M.D.

"If a person is diagnosed with a very significant illness, it is important to think about what his or her life will be like after surviving cancer," Hughes-Halbert said. "We have to take care of our bodies and our minds because those two things work together."

RICHLAND, Wash. - Marine scientists from around the world spent the last four years reviewing numerous studies and other data on the possible environmental effects of marine renewable energy (MRE) devices and found that the potential impact to marine life is likely small or undetectable.

However, scientists say there is still uncertainty around some issues, as there have been relatively few sizable deployments of MRE devices around the world where data can be collected.

The 2020 State of the Science report was released today by Ocean Energy Systems (OES)-Environmental, a collaboration under Ocean Energy Systems, supported by the International Energy Agency, and dedicated to examining the environmental effects of MRE development. The 300-page report is the most comprehensive international analysis to date on the issue. The report's release coincides with World Oceans Day and with President Trump's proclamation of June as National Ocean Month.

"We believe that small numbers of operational marine energy devices are unlikely to cause harm to marine animals, including marine mammals, fish, diving seabirds, and benthic animals; change habitats on the seafloor or in the water significantly; or change the natural flow of ocean waters or waves," said Andrea Copping, an oceanographer with the U.S. Department of Energy's Pacific Northwest National Laboratory and lead author of the report.

With the ocean covering more than 70 percent of the Earth's surface, drawing upon the power of the ocean to provide electricity would reduce the carbon footprint from energy production, provide grid stability in remote, coastal areas, and could add $3 trillion to the global economy. MRE development is also expected to create new jobs in supply chain companies and environmental consultancies.

MRE is generated from ocean waves, tides, and currents; ocean temperature and salinity gradients; and the flow of large rivers. For example, devices like wave energy converters extract the power from ocean waves and convert it into electricity. Developing a fraction of available wave energy in U.S. waters could result in clean, reliable power for millions of American homes.

The report represents the most up-to-date knowledge on environmental effects of MRE, based on studies and monitoring from publicly available, peer-reviewed scientific literature and reports. The 30 scientists who authored the report investigated potential stressors, including:

underwater noise;

electromagnetic fields;

changes in oceanographic processes, including circulation, wave height, sediment transport patterns, water quality, and marine food webs;

encounters with moorings and cables; and

the risk of a marine mammal or fish colliding with a device.

"Despite our findings, we still need more data about what might, or might not, happen to animals swimming close to operating turbines underwater. In the years to come, we will continue to focus our research on examining this issue and building our knowledge base to help progress this important renewable energy industry," Copping said.

The report can help MRE developers consider how to design, site and operate devices; avoid any impacts to marine animals and environments; provide information to government regulators; and inform the broader research community of the latest findings.

The authors reported that, with the few MRE devices deployed to date, no marine mammals, fish, or seabirds have ever been observed colliding with a device. Additionally, there was no evidence of harm from underwater noise from operational devices or electromagnetic fields emitted from electric cables; no significant changes in habitat have been caused by MRE devices; and potential changes to oceanographic systems or entanglement of marine animals with mooring systems or cables pose very low risks.

Henry Jeffrey, chair of OES, said, "This project, supported by the OES, reveals the latest thinking about the interaction of ocean energy technologies with the environment and I strongly encourage its use to help streamline consenting processes and support the responsible development of ocean energy around the world. Since the publication of our 2016 State of the Science report, our understanding of potential impacts has increased as a result of more deployments and monitoring efforts, supported by continuous collaborative efforts among OES nations under the leadership of the US Department of Energy."
The report was funded by DOE's Water Power Technologies Office and OES; more than a dozen PNNL researchers served as authors.

OES functions within a framework created by the Inter¬national Energy Agency and represents nations with an interest in developing MRE. OES-Environmental is an initiative under OES, made up of 15 countries that collaborate to evaluate the state of the science of potential environmental effects of MRE development, to assist with permitting processes, and to allow increased and responsible deployment of devices.

RENO, Nev. - New evidence identifies 64 pesticide residues in milkweed, the main food for monarch butterflies in the west. Milkweed samples from all of the locations studied in California's Central Valley were contaminated with pesticides, sometimes at levels harmful to monarchs and other insects.

The study raises alarms for remaining western monarchs, a population already at a precariously small size. Over the last few decades their overwintering numbers have plummeted to less than 1% of the population size than in the 1980s - which is a critically low level.

Monarch toxicity data is only available for four of the 64 pesticides found, and even with this limited data, 32% of the samples contained pesticide levels known to be lethal to monarchs, according to a study released today in Frontiers in Ecology and Evolution.

"We expected to find some pesticides in these plants, but we were rather surprised by the depth and extent of the contamination," said Matt Forister, a butterfly expert, biology professor at the University of Nevada, Reno and co-author of the paper. "From roadsides, from yards, from wildlife refuges, even from plants bought at stores - doesn't matter from where - it's all loaded with chemicals. We have previously suggested that pesticides are involved in the decline of low elevation butterflies in California, but the ubiquity and diversity of pesticides we found in these milkweeds was a surprise."

Milkweed was chosen as the focus of this study because it the only food source for larval monarch butterflies in the West, and thus critical for their survival.

"We collected leaf samples from milkweed plants throughout the Central Valley and sent them to be screened for pesticides," Chris Halsch, lead author of the paper and a doctoral student in the University's Ecology, Evolution, and Conservation Biology program, said. "This study is the first necessary step for understanding what butterflies are actually encountering. Now we can use these data to design experiments to test hypotheses about the relative importance of pesticide use and other stressors such as climate change on local butterflies."

While this is only a first look at the possible risks these pesticides pose to western monarchs, the findings indicate the troubling reality that key breeding grounds for western monarchs are contaminated with pesticides at harmful levels.

"One might expect to see sad looking, droopy plants that are full of pesticides, but they are all big beautiful looking plants, with the pesticides hiding in plain sight," Forister, who has been a professor int he University's College of Science since 2008, said.

Western monarchs are celebrated throughout the western states and especially along the California coast where large congregations overwinter in groves of trees. Population declines also have been documented in the breeding grounds. Areas of inland California, including the Central Valley, offer important monarch breeding habitat throughout the spring and summer, including being the home to the very first spring generation which will continue the migration inland to eventually populate all western states and even southern British Columbia.

Declines in the population of western monarch butterflies have been linked with various stressors, including habitat loss and degradation, pesticide use, and climate change, among others. While pesticide use has been associated with declines, previous studies had not attempted to quantify the residues that butterflies can encounter on the western landscape.

The study's findings paint a harsh picture for western monarchs, with the 64 different pesticides identified in milkweed. Out of a possible 262 chemicals screened, there was an average of nine types of individual pesticides per sample and as many as 25. Agricultural and retail samples generally had more residues than wildlife refuges and urban areas, but no area was entirely free from contamination. Certain pesticides were present across all landscapes, with five pesticides appearing more than 80% of the time. Chlorantraniliprole, the second most abundant compound, was found at lethal concentrations to Monarchs in 25% of all samples.

Understanding of pesticide toxicity to the monarch is limited, and is based on previously reported lab experiments. Thus we have much to learn about the concentrations encountered in field, but these new results raise concerns nonetheless. While this research focused on monarch toxicity, other pollinators and beneficial insects are also at risk from pesticide contamination throughout the landscape.

"We can all play a role in restoring habitat for monarchs," said Sarah Hoyle, Pesticide Program Specialist at the Xerces Society for Invertebrate Conservation and coauthor of the paper. "But it is imperative that farmers, land managers and gardeners protect habitat from pesticides if we hope to recover populations of this iconic animal."

Field work, gathering plant samples, was completed last spring and summer. The lab work was completed by Nicolas Baert from the Department of Entomology and manager of the Chemical Ecology Core Facility at Cornell University. Statistical computations were completed this winter by Forister and colleague James Fordyce from the Department of Ecology and Evolutionary Biology at the University of Tennessee, Knoxville.

Read the published study in Frontiers in Ecology and Evolution: Pesticide Contamination of Milkweeds Across the Agricultural, Urban, and Open Spaces of Low-Elevation Northern California.

USC researchers have discovered that an old antibiotic may be a powerful new tool against a deadly superbug, thanks to an innovative screening method that better mimics conditions inside the human body.

The antibiotic, rifabutin, is "highly active" in fighting multidrug-resistant Acinetobacter baumannii, a significant cause of life-threatening infections in medical facilities, researchers found.

The study appears today in Nature Microbiology.

"Rifabutin has been around for more than 35 years, and no one has ever studied it for Acinetobacter infections before," said first author Brian Luna, assistant professor of molecular microbiology and immunology at Keck School of Medicine of USC. "Going forward, we may find many new antibiotics that have been missed over the last 80 years because the screening tests used to discover them were suboptimal."

Rifabutin is used to treat TB, especially in people with HIV/AIDS who can't tolerate a similar drug, rifampin. It is on the World Health Organization's List of Essential Medicines, the safest and most effective medicines needed in a health system.

Until now, it hadn't been tried against Acinetobacter baumannii, which emerged during the Iraq War as a troop-killing superbug in military treatment facilities. Acinetobacter causes pneumonia, meningitis and bloodstream infections; it tends to strike patients requiring lengthy hospital stays and invasive devices like catheters and ventilators.

Each year, Acinetobacter baumannii is responsible for about 2% of the 99,000 U.S. deaths from hospital-acquired infections, according to the Centers for Disease Control and Prevention.

One reason rifabutin's superpower against superbugs was overlooked is because of current screening techniques, researchers said. Since the 1940s, new or existing antibiotics have been tested against bacteria grown in "rich culture media," a nutrient-packed broth or gel which speeds up the process by making the bacteria to grow rapidly.

"But bacteria grow very differently inside the human body," said Brad Spellberg, chief medical officer at the Los Angeles County-University of Southern California Medical Center and senior author of the study. So, the team designed a new type of "nutrient-limited" media that better mimics conditions inside the body. They hypothesized that the more realistic media might unmask antibiotics with hidden strengths.

They found that rifabutin was vigorously active against Acinetobacter baumannii grown in the nutrient-limited media (as well as in animal tissue) but not effective against bacteria grown in the more commonly used media.

The scientists discovered that rifabutin uses a unique, Trojan-horse strategy to trick the bacteria into actively importing the drug inside itself, bypassing the bacterial outer cell defenses. This "pump" that imports the drug is only active in the more human-like media. In traditional rich culture media, high levels of iron and amino acids suppress the pump's activity, researchers found.

"Rifabutin can be used immediately to treat such infections because it is already FDA-approved, cheap and generic, and on the market," Spellberg said. "But we would like to see randomized controlled human trials to prove its efficacy, so we know for sure one way or the other."

Researchers at the University of Missouri and the University of Essex in the United Kingdom found boys' poor reading skills in adolescence, combined with the social attitudes about women attending college, can help explain why fewer men than women enroll in higher education or other types of post-high school education.

Their findings were published in the Proceedings of the National Academy of Sciences.

"Reading scores are important for both boys and girls, and we know that girls, on average, score better on reading tests," said co-author David Geary, a Curators Distinguished Professor of Psychological Sciences in the College of Arts and Science.

Geary said adolescent reading scores and social attitudes toward women attending college can predict the ratio of men and women attending college or other post-secondary education.

"Here, we studied a snapshot of reading achievements for boys and girls when they were 15 years old," he said. "And with an understanding of how social attitudes are in various countries about girls going to college, we can predict the ratio of men and women attending college five years later."

Geary and his co-author Gijsbert Stoet, a professor of psychology at University of Essex, analyzed three international databases: post-secondary education enrollment data between 2011-2017 from the Organization for Economic Co-operation and Development; national reading scores for 15- and 16-year-olds from the Program for International Student Assessment; and social attitudes toward women pursuing university education from the World Values Survey. Specifically, the researchers looked at one question in the World Values Survey that read, "A university education is more important for a boy than for a girl." In total, the data represents over 400,000 boys and girls in 18 countries.

Stoet explains why social attitudes should be considered along with reading scores.

"An important factor to consider is the degree to which people across the world believe that a college education is equally important for girls as it is for boys," Stoet said. "Although more and more girls have been going to college, girls are still more likely than boys to be at a disadvantage in terms of social attitudes; this is a bigger problem in some countries than in others."

Geary said the study paints a bleak picture for reducing this gender gap -- unless reading skills are improved.

"The practical implication is that equity in college enrollment is well out of reach at this time," Geary said. "There is no good reason to expect that national reading levels for either gender will be sufficiently raised in the coming decade to change enrollment patterns. The way to counter that is to improve reading skills, but that improvement will have to start early in life. The reading gap between boys and girls is there from the very beginning of schooling, even in preschool."

CHAMPAIGN, Ill. -- Mobile apps are helping track the spread of COVID-19 to contain the outbreak, but the apps also raise concerns about personal privacy.

Information sciences professor Masooda Bashir and doctoral student Tanusree Sharma at the University of Illinois at Urbana-Champaign analyzed 50 COVID-19-related apps available in the Google Play store for their access to users' personal data and their privacy protections. Bashir and Sharma found that most of the apps required access to users' personal data, but only a handful indicated the data would be anonymous, encrypted and secured.

They report their findings in the journal Nature Medicine.

"What is disconcerting is that these apps are continuously collecting and processing highly sensitive and personally identifiable information, such as health information, location and direct identifiers (e.g., name, age, email address and voter/national identification)," they wrote in the journal article. "Governments' use of such tracking technology - and the possibilities for how they might use it after the pandemic - is chilling to many. Notably, surveillance mapping through apps will allow governments to identify people's travel paths and their entire social networks."

The functionalities of the COVID-related apps developed around the world include live maps and updates of confirmed cases, real-time location-based alerts, systems for monitoring home isolation and quarantine, direct reporting to the government of symptoms and education about COVID-19. Some also offer monitoring of vital signs, virtual medical consultations and community-driven contact tracing.

Of the 50 apps the researchers evaluated, 30 require users' permission to access data from their mobile devices such as contacts, photos, media, files, location data, the camera, the device's ID, call information, Wi-Fi connection, microphone, network access, the Google service configuration and the ability to change network connectivity and audio settings. Some of the apps state they will collect users' age, email address, phone number and postal code; the device's location, unique identifiers, mobile IP address and operating system; and the types of browsers used on the device.

Only 16 of the apps indicated such data will be anonymous, encrypted, secured and reported only in aggregate form.

Of the apps sampled, 20 were issued by governments, health ministries and other such official sources. It is not clear if the data collected by the apps is protected by laws such as the Health Insurance Portability and Accountability Act, and the U.S. doesn't have a structured privacy framework in place as Europe does, the researchers wrote.

They acknowledged that mass surveillance measures may be necessary to contain the spread of the virus.

"Health care providers must absolutely use whatever means are available to save lives and confine the spread of the virus," they wrote. "But it is up to the rest, especially those in the field of information privacy and security, to ask the questions needed to protect the right to privacy."

We tend to like people who like us--a basic human trait that psychologists have termed "reciprocity of attraction." This principle generally works well to start relationships because it reduces the likelihood of rejection. Yet, making the chase harder also has its upsides. Which one then is the better strategy for finding a partner?

A team of researchers from the University of Rochester and the Israeli-based Interdisciplinary Center Herzliya examined the effects of playing hard to get, a mating strategy that is likely to instill a certain degree of uncertainty. In a new study, published in the Journal of Social and Personal Relationships, they show that making the chase harder increased a potential mate's desirability.

The duo of Gurit Birnbaum, a social psychologist and associate professor of psychology at the IDC Herzliya, and Harry Reis, a professor of psychology and Dean's Professor in Arts, Sciences & Engineering at the University of Rochester, discovered that immediately reciprocating another person's interest may not be the smartest strategy for attracting mates.

"People who are too easy to attract may be perceived as more desperate," says Birnbaum. "That makes them seem less valuable and appealing--than those who do not make their romantic interest apparent right away."

While playing hard to get is a common strategy used to attract mates, past research has been unclear about whether, and if so, why this strategy works--which this study sought to clear up. Of course, some are reluctant to employ this strategy, worrying that it'll backfire and drive prospective partners away out of fear of being rejected.

Indeed, in previous research the duo had shown that those who feel greater certainty that a prospective romantic partner reciprocates their interest will put more effort into seeing that person again, while rating the possible date as more sexually attractive than they would if they were less certain about the prospective date's romantic intentions.

However, in their latest undertaking the team tested tactics across three interrelated studies, which gave the impression that potential partners were hard to get, signaling their "mate value" by being, for example, selective in their partner choices. Participants interacted with what they believed to be another research participant of the opposite-sex, but who was in reality an insider--a member of the research team. Next, participants rated the extent to which they felt the insider was hard to get, their perceptions of the insider's mate value (e.g., "I perceive the other participant as a valued mate"), and their desire to engage in various sexual activities with the insider.

In study 1, participants interacted with study insiders whose online profile indicated that they were either hard to get or easy to attract. The researchers discovered that participants who interacted with the more selective profile perceived the insider as more valued and therefore more desirable as a partner, compared to participants who interacted with less selective insiders (who seemed easier to attract).

In study 2, the researchers looked at the efforts invested in pursuing a potential partner and whether such efforts would inspire heightened sexual interest. Here participants were led to exert (or not) real efforts to attract the insider during face-to-face interactions. During the experiment, participants engaged in a conversation with another participant (who was in reality a study insider). The experimenter instructed participants and insiders to discuss their preferences in various life situations and presented a list of 10 questions (e.g., "To what extent do you prefer intimate recreation over mass entertainment?"; "To what extent do you like to cuddle with your partner while sleeping?"). The insider expressed a different preference from the participants to seven out of the 10 questions.

Participants in the hard-to-get group were told to try and resolve their disagreements. Using a fixed script, the insiders gradually allowed themselves "to be convinced" by the participants and eventually expressed agreement with the participant's position. That way, the researchers tried to make participants feel that they had invested efforts and that their efforts were eventually successful.

In the no-effort group, participants were instructed only to express their preferences and explain their point of view without trying to resolve the differences. That way participants didn't feel that the discussion involved exerting efforts to convince the insider. The team found that not only selectiveness but also efforts invested in the pursuit of a mate rendered potential partners more valuable and sexually desirable than those were little effort was exerted.

In study 3, interactions unfolded spontaneously and were coded for efforts undertaken by participants to see the insider again. Here the researchers examined whether being hard to get would increase not only prospective partners' sexual desirability but also the efforts devoted to seeing them in the future. To do so, participants conversed with the insider via Instant Messenger in a chat. At the end, participants were asked to leave one final message for the insider.

Next, the research team coded these messages for efforts made to interact again with the insider by counting in each message participants' expressions of romantic interest and desire for future interaction--for example, complimenting the insider, flirting with him/her, asking him/her for a date. The team found that interacting with prospective partners who were perceived as hard to get not only enhanced their mate value and desirability but was also translated into investment of concrete efforts to see them again.

Findings

A person who is perceived as hard to get is associated with a greater mate value

Study participants made greater efforts on/and found more sexually desirable those potential dates they perceived as hard to get

Study participants made greater efforts to see those again for whom they had made efforts in the first place

Says Reis, "We all want to date people with higher mate value. We're trying to make the best deal we can."

Of course, some may be reluctant to employ this scarcity strategy, worrying that it'll drive prospective partners away out of fear of being rejected.

Reis acknowledges the strategy doesn't work for everyone, all the time. "If playing hard to get makes you seem disinterested or arrogant," he says, "it will backfire."

So, how then do you reconcile these two approaches--playing hard to get on one hand and removing uncertainty on the other?

Show initial interest in potential partners so as not to alienate them, advises Birnbaum. Yet, don't reveal too much about yourself. People are "less likely to desire what they already have," she explains. Instead, build a connection with a potential partner gradually, thereby creating "a sense of anticipation and a desire to learn more about the other person."

Playing hard to get may work as long as potential partners feel that their efforts are likely to be successful--eventually.

Monkeys can overcome their aversion to animated monkeys through a more realistic avatar, according to research recently published in eNeuro.

Humans feel more comfortable toward life-like humanoid robots, but if a robot gets too life-like, it can become creepy. This "uncanny valley" effect plagues monkeys, too, which becomes a problem when scientists use animated monkey faces to study social behavior. However, monkeys overcome the uncanny valley when presented with a sufficiently realistic monkey avatar created using movie industry animation technology.

Siebert et al. compared how Rhesus monkeys reacted toward five types of monkey faces: video footage from real monkeys, a natural looking avatar with fur and facial details, a furless avatar, a greyscale avatar, and a wireframe face. The monkeys looked at the wireframe face but avoided looking at the furless and greyscale avatars, showing the uncanny valley effect at work. However, the natural looking avatar with fur overcame this effect. The monkeys looked at the model and made social facial expressions, comparable to how they would act around real monkeys. Using this type of avatar will make social cognition studies more standardized and replicable.

By developing a lab-engineered model of the human blood-brain barrier (BBB), neuroscientists at MIT's Picower Institute for Learning and Memory have discovered how the most common Alzheimer's disease risk gene causes amyloid protein plaques to disrupt the brain's vasculature and showed they could prevent the damage with medications already approved for human use.

About 25 percent of people have the APOE4 variant of the APOE gene, which puts them at substantially greater risk for Alzheimer's disease. Almost everyone with Alzheimer's, and even some elderly people without, suffer from cerebral amyloid angiopathy (CAA), a condition in which amyloid protein deposits on blood vessel walls impairs the ability of the BBB to properly transport nutrients, clear out waste and prevent the invasion of pathogens and unwanted substances.

In the new study, published June 8 in Nature Medicine, the researchers pinpointed the specific vascular cell type (pericytes) and molecular pathway (calcineurin/NFAT) through which the APOE4 variant promotes CAA pathology.

The research indicates that in people with the APOE4 variant, pericytes in their vessels churn out too much APOE protein, explained senior author Li-Huei Tsai, Picower Professor of Neuroscience and director of the Picower Institute. APOE causes amyloid proteins, which are more abundant in Alzheimer's disease, to clump together. Meanwhile, the diseased pericytes' increased activation of the calcineurin/NFAT molecular pathway appears to encourage the elevated APOE expression.

There are already drugs that suppress the pathway. Currently they are used to subdue the immune system after a transplant. When the researchers administered some of those drugs, including cyclosporine A and FK506, to the lab-grown BBBs with the APOE4 variant, they accumulated much less amyloid than untreated ones did.

"We identify that there is a specific genetic pathway that is expressed differently in a population that is susceptible to Alzheimer's disease," said study lead author Joel Blanchard, a postdoc in Tsai's lab. "By identifying this we could identify drugs that change this pathway back to a non-diseased state and correct this outcome that's associated with Alzheimer's."

Building barriers

To investigate the connection between Alzheimer's, the APOE4 variant and CAA, Blanchard, Tsai and co-authors coaxed human induced pluripotent stem cells to become the three types of cells that make up the BBB: brain endothelial cells, astrocytes and pericytes. Pericytes were modeled by mural cells that they tested extensively to ensure they exhibited pericyte-like properties and gene expression.

Grown for two weeks within a three-dimensional hydrogel scaffold, the BBB model cells assembled into vessels that exhibited natural BBB properties, including low permeability to molecules and expression of the same key genes, proteins and molecular pumps as natural BBBs. When immersed in culture media high in amyloid proteins, mimicking conditions in Alzheimer's disease brains, the lab-grown BBB models exhibited the same kind of amyloid accumulation seen in human disease.

With a model BBB established, they then sought to test the difference APOE4 makes. They showed by several measures that APOE4-carrying BBB models accumulated more amyloid from culture media than those carrying APOE3, the more typical and healthy variant.

To pinpoint how APOE4 makes that difference, they engineered eight different versions covering all the possible combinations of the three cell types having either APOE3 or APOE4. When exposed these month-old models to amyloid-rich media, only versions with APOE4 pericyte-like mural cells showed excessive accumulation of amyloid proteins. Replacing APOE4 mural cells with APOE3-carrying ones reduced amyloid deposition. These results put blame for CAA-like pathology squarely on pericytes.

To further validate the clinical relevance of these findings, the team also looked at APOE expression in samples of human brain vasculature in the prefrontal cortex and the hippocampus, two regions crucially affected in Alzheimer's disease. Consistent with the team's lab BBB model, people with APOE4 showed higher expression of the gene in the vasculature, and specifically in pericytes, than people with APOE3.

"That is a salient point of this paper," said Tsai, a founding member of MIT's Aging Brain Initiative. "It's really cool because it stresses the cell-type specific function of APOE."

A pathway toward treatment?

The next step was to determine how APOE4 becomes so overexpressed by pericytes. The team therefore identified hundreds of transcription factors - proteins that determine how genes are expressed - that were regulated differently between APOE3 and APOE4 pericyte-like mural cells. Then they scoured that list to see which factors specifically impact APOE expression. A set of factors that were upregulated in APOE4 cells stood out: ones that were part of the calcineurin/NFAT pathway. They observed similar upregulation of the pathway in pericytes from human hippocampus samples.

As part of their investigation of whether elevated signaling activity of this pathway caused increased amyloid deposition and CAA, they tested cyclosporine A and FK506 because they tamp pathway activity down. They found that the drugs reduced APOE expression in their pericyte-like mural cells and therefore APOE4-mediated amyloid deposits in the BBB models. They also tested the drugs in APOE4-carrying mice and saw that the medicines reduced APOE expression and amyloid buildup.

Blanchard and Tsai noted that the drugs can have significant side effects, so their findings might not suggest using exactly those drugs to address CAA in patients.

"Instead it points toward the value of understanding the mechanism," Blanchard said. "It allows one to design a small molecule screen to find more potent drugs that have less off-target effects."

The three-dimensional structure of the human genome is essential for providing a rapid and robust inflammatory response but is surprisingly not vital for reprogramming one cell type into another, according to research published today in Nature Genetics. The findings shed new light on the fundamental relationship between how a genome folds and the function of a cell.

Each human cell has two metres of genome condensed down into 10 microns within the nucleus. Folding the genome is more than a packaging solution, it helps genes make physical contact with other genes or a regulatory element that may be located quite a distance away along the chromosome. This is crucial for cell function.

The precise 3D structure of the genome is weaved together by architectural proteins. CTCF is one of the most prominent of these structural proteins. Collectively, it helps to shape the overall three-dimensional structure of the genome, which is why CTCF has been shown to be essential for embryonic development, DNA repair and cell cycles, as well as many other vital processes that make it an intensive area of research.

"If you think of the structure of the genome as a house, CTCF is the scaffold dividing the space in rooms and shaping the building," says Thomas Graf, senior author of the study and Group Leader at the Centre for Genomic Regulation in Barcelona. "Studying CTCF helps us understand the glue that holds the genome together, and by proxy the role of 3-D genomic architecture in various fundamental processes in life."

CTCF's role in transdifferentiation is particularly controversial. This is when a cell reprograms itself into another type of cell without undergoing an intermediate state, such as pancreatic alpha cells turning into insulin-secreting beta cells after injury of the pancreas.

To study this, researchers at the Centre for Genomic Regulation (CRG) in Barcelona developed a unique system where human B cells can be induced into becoming macrophages. To uncover CTCF's role in this process they used CRISPR genome editing tools to degrade the protein and study changes in genome organisation as the cell fate changes.

"To our great surprise, cell transdifferentiation continues to take place with or without CTCF, even though the shape of the human genome changed" says Thomas. "Answering one question has led to another. What are the other factors that participate to the 3D architecture of the human genome that are essential for one cell to turn into another?"

Importantly, the researchers also found that CTCF depletion impairs a cell's ability to have a full-blown inflammatory response in the presence of bacterial endotoxin. It is one of the first instances in which researchers have discovered a link between 3-D genome architecture and inflammation.

"The findings of our study could help us understand why an inflammatory response is impaired or exaggerated in some situations. In the far future it might even be used to module the inflammatory response," says Gregoire Stik, first author of the paper and postdoctoral researcher at the Centre for Genomic Regulation. "We've known about CTCF for decades yet we're still uncovering its true role in genome shape and cell function. There are many more mysteries folded deep in the genome yet to discover."