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Scientists at the Center for Infection and Immunity (CII) at Columbia University Mailman School of Public Health, the U.S. Centers for Disease Control and Prevention (CDC), and the University of California San Diego report antibody evidence in cerebrospinal fluid (CSF) that points to enterovirus (EV) infection as a cause for acute flaccid myelitis (AFM), a disease responsible for partially paralyzing more than 560 children in the United States since 2014. Results of the study appear in the journal mBio.

AFM patients, upwards of 90 percent of whom are children, present with severe weakness in one or more limbs, usually within a month of a respiratory or gastrointestinal illness, leading clinicians and scientists to posit that a pathogen is behind AFM. A preliminary CDC analysis found that more than 40 percent of children with AFM had evidence of EV RNA in respiratory or fecal samples. Yet in CSF, they found EV in only 4 of 567 total confirmed cases.

In the new study, researchers reexamined the CSF of ASM patients for signs of EV using two methods. First, they analyzed CSF from 14 AFM and 5 non-AFM patients with central nervous system diseases using a specialized high throughput sequencing technology developed by CII called VirCapSeq-VERT. They found EV RNA in only one adult AFM case and one non-AFM case. Next, CSF samples and blood serum from cases and controls were tested for antibodies to EVs using high density peptide microarrays that represent the capsid proteins of all species of human EV (EV-A, EV-B, EV-C, and EV-D). Researchers found antibodies to EV peptides in 11 of 14 AFM patients (79 percent), significantly higher than non-AFM controls (1 patient, 20 percent). Six of 14 CSF (43 percent) and 8 of 11 blood sera (73 percent) from AFM patients were immunoreactive to an EV-D68-specific peptide, whereas no controls were immunoreactive in either CSF or sera. The researchers also tested CSF from the 14 individuals with AFM and six controls for evidence of tick-borne diseases (TBD) using the TBD Serochip, a test developed by CII to simultaneously detect antibodies to eight tick-borne pathogens. They found no evidence of TBD pathogens.

"Physicians and scientists have long suspected that enteroviruses, a family of viruses responsible for polio, another paralyzing disease, are behind AFM, but there has been little evidence to support this idea," says co-lead investigator Nischay Mishra, PhD, assistant professor of epidemiology at CII. "Further work is needed with larger, prospective studies; nonetheless, these results take us one step closer to understanding the cause of AFM, and one step closer to developing diagnostic tools and treatments."

"Pathogen discovery has historically focused on direct detection of infectious agents. The introduction of new methods that allow us to also test for footprints of exposure will lead to new insights into infectious diseases," says co-senior author Ian Lipkin, MD, director of CII.

RIVERSIDE, Calif. -- Alzheimer's disease, the most common cause of dementia among the elderly, is characterized by plaques and tangles in the brain, with most efforts at finding a cure focused on these abnormal structures. But a University of California, Riverside, research team has identified alternate chemistry that could account for the various pathologies associated with the disease.

Plaques and tangles have so far been the focus of attention in this progressive disease that currently afflicts more than 5.5 million people in the United States. Plaques, deposits of a protein fragment called beta-amyloid, look like clumps in the spaces between neurons. Tangles, twisted fibers of tau, another protein, look like bundles of fibers that build up inside cells.

"The dominant theory based on beta-amyloid buildup has been around for decades, and dozens of clinical trials based on that theory have been attempted, but all have failed," said Ryan R. Julian, a professor of chemistry who led the research team. "In addition to plaques, lysosomal storage is observed in brains of people who have Alzheimer's disease. Neurons -- fragile cells that do not undergo cell division -- are susceptible to lysosomal problems, specifically, lysosomal storage, which we report is a likely cause of Alzheimer's disease."

Study results appear in ACS Central Science, a journal of the American Chemical Society.

An organelle within the cell, the lysosome serves as the cell's trashcan. Old proteins and lipids get sent to the lysosome to be broken down to their building blocks, which are then shipped back out to the cell to be built into new proteins and lipids. To maintain functionality, the synthesis of proteins is balanced by the degradation of proteins.

The lysosome, however, has a weakness: If what enters does not get broken down into little pieces, then those pieces also can't leave the lysosome. The cell decides the lysosome is not working and "stores" it, meaning the cell pushes the lysosome to the side and proceeds to make a new one. If the new lysosome also fails, the process is repeated, resulting in lysosome storage.

"The brains of people who have lysosomal storage disorder, another well-studied disease, and the brains of people who have Alzheimer's disease are similar in terms of lysosomal storage," Julian said. "But lysosomal storage disorder symptoms show up within a few weeks after birth and are often fatal within a couple of years. Alzheimer's disease occurs much later in life. The time frames are, therefore, very different."

Julian's collaborative team of researchers in the Department of Chemistry and the Division of Biomedical Sciences at UC Riverside posits that long-lived proteins, including beta-amyloid and tau, can undergo spontaneous modifications that can make them undigestible by the lysosomes.

"Long-lived proteins become more problematic as we age and could account for the lysosomal storage seen in Alzheimer's, an age-related disease," Julian said. "If we are correct, it would open up new avenues for treatment and prevention of this disease."

He explained that the changes occur in the fundamental structure of the amino acids that make up the proteins and are the equivalent of flipping the handedness of the amino acids, with amino acids spontaneously acquiring the mirror images of their original structures.

"Enzymes that ordinarily break down the protein are then not able to do so because they are unable to latch onto the protein," Julian added. "It's like trying to fit a left-handed glove on your right hand. We show in our paper that this structural modification can happen in beta-amyloid and tau, proteins relevant to Alzheimer's disease. These proteins undergo this chemistry that is almost invisible, which may explain why researchers have not paid attention to it."

Julian explained these spontaneous changes in protein structure are a function of time, taking place if the protein hangs around for too long.

"It's been long known that these modifications happen in long-lived proteins, but no one has ever looked at whether these modifications could prevent the lysosomes from being able to break down the proteins," he said. "One way to prevent this would be to recycle the proteins so that they are not sitting around long enough to go through these chemical modifications. Currently, no drugs are available to stimulate this recycling -- a process called autophagy -- for Alzheimer's disease treatment."

The research was done in collaboration with Byron D. Ford, a professor of biomedical sciences in the School of Medicine. The findings could have implications for other age-related diseases such as macular degeneration and cardiac diseases linked to lysosomal pathology.

“This collaboration between laboratories in our distinct research fields provides us a unique opportunity to explore novel mechanisms and potential treatment targets for Alzheimer’s disease and other neurodegenerative disorders,” Ford said.

Julian and Ford were joined in the research by Tyler R. Lambeth (co-first author), Dylan L. Riggs (co-first author), Lance E. Talbert, Jin Tang, Emily Coburn, Amrik S. Kang, Jessica Noll, and Catherine Augello.

Next, the team will examine the extent of the protein modifications in human brains as a function of age. The researchers will study brains of people with Alzheimer's disease as well as of people not afflicted by it.

Since 2011, the Population Study of Chinese Elderly in Chicago (PINE), the most extensive epidemiological cohort study of Chinese older adults in the United States, has revealed critical health disparities among the growing Chinese American population.

In the current issue of the Journal of the American Geriatrics Society (JAGS), 17 new research papers from the PINE Study present an unprecedented exploration of cultural factors concerning Chinese Americans' health. The papers also draw data from the Filial Piety Study, a study of the PINE Study participants' adult children. The resulting research provides comprehensive, multigenerational insight into the lives of Chinese Americans.

"Despite the size and substantial growth of the Chinese American community, quality health data on this vulnerable population remains critically inadequate," said XinQi Dong, director of Rutgers University's Institute for Health, Health Care Policy and Aging Research and the lead researcher of the PINE and PIETY studies. "This collection of JAGS articles helps provide the context and understanding necessary to improve the health of Asian populations through education, research, advocacy, policy, and sustainable community engagement and promote greater health equity among all minority groups."

For the PINE Study, researchers looked at more than 3,000 Chinese Americans aged 60 and older to better understand their current experiences, offer solutions for improving the research participation of minority older adults, and reduce health disparities.

The Filial Piety Study assessed the health and well-being of 548 PINE Study participants' adult children aged 21 and older. The study revealed widespread psychological and social stressors associated with the growing problems of caregiving distress and burden and intergenerational conflict among the Chinese American adult community.

"While preliminary research indicates marked disparities concerning Chinese Americans' health and well-being, numerous factors prevent quality research from being conducted and disseminated," said Dong. Barriers to research include a reluctance by Chinese Americans to participate in federally-sponsored activities, linguistic and cultural barriers, a lack of federal funding, and the tendency of federal-level health researchers to aggregate data of diverse Asian groups under the same racial category.

Researchers must also contend with the "model minority" myth - the perception that U.S. Asians are generally economically prosperous and healthy, and enjoy active social and familial relationships.

The articles -- organized into the themes of data collection methods, elder abuse, cognitive function, psychological well-being, social relationships, and health behaviors -- navigate the many challenges to studying this vulnerable population and address the insufficiency of health and wellness data.

The first article discusses methods of data collection, detailing how researchers used a custom web application to conduct in-person, native-language surveys of participants. The application not only helped overcome some of the barriers in health disparity research but also improved participation and retention.

Four articles addressing elder abuse examine the risk factors and consequences of violence across the life course. The articles explain the link between elder abuse -- psychological abuse, physical abuse, caregiver neglect, and financial exploitation -- and
poor physical and mental health, chronic pain, greater use of healthcare services, and increased risk of mortality among older Chinese Americans.

Four articles that investigate cognitive function in the context of immigration, psychological distress, social engagement, and oral health are the first of their kind in the U.S. Chinese population. The articles emphasize the need for further study of this population's cognitive function later in life.

Three articles explore how the psychological well-being of Chinese older adults relates to physical health over time. The researchers establish a link between depressive symptoms and comorbid health conditions and demonstrate the need for emphasized screening for depression risk factors and the development of intervention strategies to proactively prevent the onset of disability.

Three articles address older Chinese immigrants' social relationships, exploring the impact of family relationships on health and wellness, filial obligations and caregiving burdens, and social engagement.

Two articles analyze patterns of health behaviors among Chinese older adults to understand potential predictors and consequences of specific health behaviors.

Key findings:

Abuse is prevalent in the Chinese American community, with 11.4% of study respondents reporting child abuse, 6.5% reporting intimate partner violence, and 15.2% reporting elder abuse.

Individuals with a history of child abuse were four times likelier to experience intimate partner violence and psychological elder abuse.

A history of psychological, intimate partner violence correlates with eight times the risk of re-experiencing psychological abuse as older adults.

Intimate partner violence was associated with five to eight times the risk for psychological elder abuse, six to nine times the risk for physical/sexual abuse, and three times the risk for financial exploitation.

Individuals with a history of childhood physical/sexual abuse experienced two times the risk of re-experiencing physical/sexual intimate partner violence. Those with a history of physical/sexual intimate partner violence faced nine times higher risks of re-experiencing physical/sexual elder abuse.

All subtypes of elder abuse were associated with a substantially increased risk of 1-, 3-, and 4-year mortality.

41.5% of Asian Americans reported not receiving annual oral health examinations, which links to decreased quality of life, depression, hypertension, poor cognition, and cognitive decline.

Approximately 50% and 54% of U.S. Chinese older adults experience various levels of functional disability and depressive symptoms, respectively.

Comorbid depression is associated with a six-fold higher likelihood of functional disability, a 70% increase in overall medical costs, and a 2.4-fold increase in mortality than those without depression.

More than 84% of Chinese American study participants had one or more chronic medical conditions, and more than 60% had two or more.

25% of older Chinese men are current smokers compared with only 8.8% among the general US population aged 65 and older.

"A growth rate almost four times higher than that of the overall U.S. older adult population necessitates a thorough understanding of older Chinese Americans' health needs," said Dong. This research will help promote healthy aging adequately, prevent health disparities, and inform the development of culturally sensitive healthcare."

The new-generation sequencing technology has ushered in a new era in medicine, making it easier to identify a sequence of nucleotides in the DNA or a sequence of amino acids in the proteins of a specific individual and use this information for both diagnosis and treatment. Minute alterations in these sequences, mutations can be indicative of a minor disorder and, sometimes, a grave disease.

Scientists from Skoltech, the Technical University of Munich, St. Petersburg Polytechnic University and the Indian Institute of Technology Madras (Chennai, India) developed a machine-learning-based method that allows analyzing the atomic structures of proteins and predicting the pathogenicity of mutations. The method is adapted for transmembrane proteins that account for 25-30% of all the proteins in a cell and often serve as targets for drugs.

"In this study, we used a combination of 1D information on the amino acid sequences of proteins and 3D information on the protein's atomic structures to create an effective machine-learning-based model that helps identify disease-associated amino acid substitutions in membrane proteins," says the first author of the study and Assistant Professor at Skoltech, Petr Popov.

LOUISVILLE, Ky. -- Everywhere you go there are stormwater detention basins built near large construction projects intended to control the flow of rainwater and runoff. Now, those basins might help in controlling nitrogen runoff into rivers and lakes, according to Lauren E. McPhillips, assistant professor of civil and environmental engineering at Penn State.

Speaking today (Aug. 12) at the annual meeting of the Ecological Society of America in Louisville, Kentucky, she explained that she and colleagues at Cornell University looked at stormwater detention basins in the area around Ithaca, New York.

"Part of the goal for stormwater detention basins is to manage flow," said McPhillips. "Increasingly, we are trying to get more water quality goals out of them."

Controlling runoff from rain and trapping sediment has always been a goal of these ubiquitous basins, but new techniques may make them suitable for removing nitrate from the water as well. The basins the researchers examined are in urban and suburban areas, and nitrate comes from atmospheric deposition on roads, car combustion and lawn fertilizers.

"These basins have always been treated as black boxes looking at water in and percentage efficiency," said McPhillips. "However, different designs of these basins perform differently, and now we are looking at performance and specific mechanisms for removal of nitrogen."

Nitrogen is the target because, while our atmosphere is composed of 78% gaseous nitrogen, other forms of the element like nitrate cause overgrowth of algae in bodies of water. This eutrophication removes oxygen from the water and creates underwater deserts where fish and other water creatures cannot live.

In general, stormwater basins are either wet basins or dry basins. Water passes through dry basins in a few days, while wet basins have standing water for much longer. A variety of things can happen to the nitrate in the basin. It can pass into the groundwater and then to rivers, streams and lakes; it can be taken up by vegetation; or it can be converted to other compounds by microbes living in the basins.

While decay of basin vegetation places the nitrate back into the basin and the groundwater, some microbial assemblages can convert nitrate all the way to gaseous nitrogen, removing it. The researchers sampled the basins and checked microbial DNA for a gene that can allow conversion of nitrate to nitrogen gas. This gene produces an enzyme that can convert nitrate into gaseous nitrogen.

"Typically, the basins are designed to be dry, but as sediment from runoff and vegetation that grows in the basins builds up, they can become wet basins," said McPhillips.

They found that the capability of producing gaseous nitrogen was higher in wet basins than dry basins. However, they also found that partial conversion produced nitrous oxides and that consumption of organic matter produces methane, both greenhouse gases. The wet basins showed higher levels of the gene that allows complete conversion of nitrate to gaseous nitrogen.

According to McPhillips, designing the basins to hold water from the beginning could decrease production of nitrous oxides, because the longer the basins hold the water, the more complete the conversion from nitrate to gaseous nitrogen.

As for the methane, McPhillips suggests that engineering the basins so that the water retention layer is below ground and not on the surface of the basin could prevent the methane from releasing into the atmosphere. Trapped in the soil, oxygen would degrade the methane.

McPhillips is now looking at stormwater retention basins on Penn State's University Park campus for further research.

Brooklyn, NY – A breakthrough study by a SUNY Downstate Health Sciences University research team has identified a specific antibody target implicated in neuropsychiatric symptoms of lupus. These symptoms, including cognitive impairment, mood disorders, seizures, headaches and psychosis, are among the most prevalent manifestations of the disease and occur in as many as 80% of adults and 95% of children with lupus. The Lupus Foundation of America estimates that more than 1.5 million Americans and 5 million people worldwide suffer from some form of lupus, with 90% of cases affecting women.

The study, Neuronal BC RNA Transport Impairments Caused by Systemic Lupus Erythematosus Antibodies, was published today in the Journal of Neuroscience.

The study identified antibodies that are directed at regulatory brain cytoplasmic RNAs (BC ribonucleic acid) that are unique to lupus patients. In layman’s terms, these antibodies disrupt these regulators of protein synthesis that allow synapses in the brain to control how they receive, store and recall information. Because these antibodies are unique in the brains of lupus patients, the study suggests that this is at the root of neuropsychiatric symptoms seen in these patients.

“Prior to this study, we poorly understood why lupus affects the brain in the way in which it does and causes neurocognitive symptoms,” said Principle Investigator Henri Tiedge, PhD, Distinguished Professor, The Robert F. Furchgott Center for Neural and Behavioral Science at SUNY Downstate. “Because we could not treat the cause, the only alternative was for physicians to treat the symptoms with anti-inflammatory drugs, immunosuppressives and other therapies, depending on the how the brain was being affected.”

According to Dr. Tiedge, the discovery gives new insight into both how and why many lupus patients suffer from these symptoms, and, just as important, may well provide the basic understanding necessary for scientists to pursue effective treatments.

“Now that we appear to have an understanding of what is causing at least some of these neuropsychiatric affects, we can turn our attention to finding treatments that target the disease process itself and will block or repress these antibodies from causing the molecular disruptions.”

“Women of color are three times more likely to be diagnosed with lupus and are much more likely to develop the disease at a younger age. Additionally, when diagnosed, women of color often have more serious complications and significantly higher death rates,” said Wayne J. Riley, M.D., President of SUNY Downstate Health Sciences University. “Not only does this discovery by Dr. Tiedge and colleagues break new ground in our understanding of lupus, but it is also especially important to the diverse communities we serve here in Brooklyn.”

In addition to Dr. Tiedge, other investigators include Ilham A. Muslimov, MD, PhD; Anna Iacoangeli, PhD; Taesun Eom, PhD; Anne Ruiz, PhD; Ellen M. Ginzler, MD; MPH, Stacy Stephenson, AAS; RLATg, and Madisen Lee, Volunteer. The study was a collaboration between both basic science and clinical researchers at SUNY Downstate Health Sciences University, including both The Robert F. Furchgott Center for Neural and Behavioral Science and the SUNY Downstate Division of Rheumatology.

About SUNY Downstate Health Sciences University

SUNY Downstate Health Sciences University is the borough’s only academic medical center for health education, research, and patient care, and is a 342-bed facility serving the healthcare needs of New York City, and Brooklyn’s 2.6 million residents. University Hospital of Brooklyn (UHB) is Downstate’s teaching hospital, backed by the expertise of an outstanding medical school and the research facilities of a world-class academic center. More than 800 physicians, representing 53 specialties and subspecialties—many of them ranked as tops in their fields—comprise Downstate's staff.

A regional center for cardiac care, neonatal and high-risk infant services, pediatric dialysis, and transplantation, SUNY Downstate also houses a major learning center for children with physical ailments or neurological disorders. In addition to UHB, SUNY Downstate comprises a College of Medicine, College of Nursing, School of Health Professions, a School of Graduate Studies, a School of Public Health, and a multifaceted biotechnology initiative, including the SUNY Downstate Biotechnology Incubator and BioBAT for early-stage and more mature companies, respectively. For more information, visit www.downstate.edu or follow us on Twitter at @sunydownstate.

Beta-amyloid plaques, the protein aggregates that form in the brains of Alzheimer's patients, disrupt many brain functions and can kill neurons. They can also damage the blood-brain barrier -- the normally tight border that prevents harmful molecules in the bloodstream from entering the brain.

MIT engineers have now developed a tissue model that mimics beta-amyloid's effects on the blood-brain barrier, and used it to show that this damage can lead molecules such as thrombin, a clotting factor normally found in the bloodstream, to enter the brain and cause additional damage to Alzheimer's neurons.

"We were able to show clearly in this model that the amyloid-beta secreted by Alzheimer's disease cells can actually impair barrier function, and once that is impaired, factors are secreted into the brain tissue that can have adverse effects on neuron health," says Roger Kamm, the Cecil and Ida Green Distinguished Professor of Mechanical and Biological Engineering at MIT.

The researchers also used the tissue model to show that a drug that restores the blood-brain barrier can slow down the cell death seen in Alzheimer's neurons.

Kamm and Rudolph Tanzi, a professor of neurology at Harvard Medical School and Massachusetts General Hospital, are the senior authors of the study, which appears in the journal Advanced Science. MIT postdoc Yoojin Shin is the paper's lead author.

Barrier breakdown

The blood vessel cells that make up the blood-brain barrier have many specialized proteins that help them to form tight junctions -- cellular structures that act as a strong seal between cells.

Alzheimer's patients often experience damage to brain blood vessels caused by beta-amyloid proteins, an effect known as cerebral amyloid angiopathy (CAA). It is believed that this damage allows harmful molecules to get into the brain more easily. Kamm decided to study this phenomenon, and its role in Alzheimer's, by modeling brain and blood vessel tissue on a microfluidic chip.

"What we were trying to do from the start was generate a model that we could use to understand the interactions between Alzheimer's disease neurons and the brain vasculature," Kamm says. "Given the fact that there's been so little success in developing therapeutics that are effective against Alzheimer's, there has been increased attention paid to CAA over the last couple of years."

His lab began working on this project several years ago, along with researchers at MGH who had engineered neurons to produce large amounts of beta-amyloid proteins, just like the brain cells of Alzheimer's patients.

Led by Shin, the researchers devised a way to grow these cells in a microfluidic channel, where they produce and secrete beta-amyloid protein. On the same chip, in a parallel channel, the researchers grew brain endothelial cells, which are the cells that form the blood-brain barrier. An empty channel separated the two channels while each tissue type developed.

After 10 days of cell growth, the researchers added collagen to the central channel separating the two tissue types, which allowed molecules to diffuse from one channel to the other. They found that within three to six days, beta-amyloid proteins secreted by the neurons began to accumulate in the endothelial tissue, which led the cells to become leakier. These cells also showed a decline in proteins that form tight junctions, and an increase in enzymes that break down the extracellular matrix that normally surrounds and supports blood vessels.

As a result of this breakdown in the blood-brain barrier, thrombin was able to pass from blood flowing through the leaky vessels into the Alzheimer's neurons. Excessive levels of thrombin can harm neurons and lead to cell death.

"We were able to demonstrate this bidirectional signaling between cell types and really solidify things that had been seen previously in animal experiments, but reproduce them in a model system that we can control with much more detail and better fidelity," Kamm says.

Plugging the leaks

The researchers then decided to test two drugs that have previously been shown to solidify the blood-brain barrier in simpler models of endothelial tissue. Both of these drugs are FDA-approved to treat other conditions. The researchers found that one of these drugs, etodolac, worked very well, while the other, beclomethasone, had little effect on leakiness in their tissue model.

In tissue treated with etodolac, the blood-brain barrier became tighter, and neurons' survival rates improved. The MIT and MGH team is now working with a drug discovery consortium to look for other drugs that might be able to restore the blood-brain barrier in Alzheimer's patients.

"We're starting to use this platform to screen for drugs that have come out of very simple single cell screens that we now need to validate in a more complex system," Kamm says. "This approach could offer a new potential form of Alzheimer's treatment, especially given the fact that so few treatments have been demonstrated to be effective."

BLOOMINGTON, Ind. -- A new study led by researchers at Indiana University has found that women and older adults who use multiple prescription drugs are significantly more likely to be prescribed pills whose combination produces dangerous side effects.

The analysis, conducted in the Brazilian health care system and recently published in the journal npj Digital Medicine, revealed a 60 percent increased risk for adverse drug reaction in women compared to men -- and a 90 percent increased risk in cases of medicines whose interaction is known to produce dangerous reactions. In older people, one in every four people prescribed multiple medicines over age 55 received drugs with an interaction -- reaching one in every three for ages 70 to 79.

total of 181 drug combinations prescribed against recommendations were uncovered. These medications, widely known to interact dangerously, were dispensed to 15,527 people among the study's population, including 5,000 who got drug combinations known to cause major complications likely requiring medical attention.

"These results are surprising -- shocking even -- since it's no secret these drugs aren't supposed to be prescribed in combination," said Luis Rocha, a professor in the IU School of Informatics, Computing and Engineering, who is the senior author on the study. "We expected some elevated risk in the elderly since they use more medications, but not this high. The gender bias was completely unexpected."

According to the U.S. Department of Health and Human Services, about one out of every three hospital visits annually are related to adverse drug effects, which include adverse drug reactions. Another analysis of adverse drug reaction in Ontario, Canada, placed the cost of these incidents at nearly $12 million per year -- or $1 per capita -- for that province alone. In other countries, such as the U.S., the IU-led study's authors estimate costs could run as much as seven times higher per capita.

The new analysis is based upon health records from Blumenau, a city in Brazil with a population of about 334,000. The researchers stumbled across gender- and age-based disparities in care during a general analysis of drug interactions among the city's population in collaboration with researchers at the Regional University of Blumenau, which developed the city's health record system. A Ph.D. student in Rocha's lab at the time of the study, Rion Brattig Correia, previously managed the lab that created the system.

The drugs identified as most commonly prescribed in dangerous combinations were standard medications -- such as omeprazole, a common heartburn medication whose brand names include Prilosec; fluoxetine, a common antidepressant whose brand names include Prozac; and ibuprofen, a common analgesic -- as well as some less common drugs, such as erythromycin, an anti-infectant.

The researchers were careful to control for other factors that might result in higher risk for dangerous drug combinations, such as older adults taking more prescription drugs, Rocha said. The study compared drugs actually prescribed to older patients against a random selection of drugs common among older adults, for example, to show that dangerous drug combinations actually occurred at a higher rate in real life compared to the random model.

Although the research did not explore the cause of these higher drug interaction risks, the lack of options for certain medications under Brazil's public health system could play a role, Rocha added. Women tend to be prescribed more antidepressants, for example, and more expensive options with fewer interactions are not available in the public health system. Similarly, older adults tend to use more medications to control cholesterol, another drug type with few public options found to occur often in dangerous combination.

"It might simply be that no other choice exists, so doctors feel that the treatment is worth the risks," Rocha said. "Or some physicians may simply be unaware of the dangers."

The researchers are hopeful the work might influence health policy in Brazil, Correia added, including increasing publicly available drug choices for seniors and women. He plans to delve further into the results to learn the deeper causes of these biases against women and older adults.

"Physicians and other health care professions everywhere need to understand the role of gender and age toward the risk of dangerous drug interactions for their patients," he said. "We expect these results will increase this awareness."

An international team of scientists, including a professor of chemistry from the University of Bristol, has worked out a way to improve energy storage devices called supercapacitors, by designing a new class of detergents chemically related to laxatives.

Their paper, published today in the journal Nature Materials, explains why these detergents, called ionic liquids, are better electrolytes than current materials and can improve supercapacitors.

Currently, aqueous and organic electrolytes are used, but more recently, researchers and manufacturers have been testing ionic liquids instead to boost performance.

Although ionic liquids are salts, at room temperature they are surprisingly not crystalline solids - as their name suggests they are in fact liquids.

This gives ionic liquids numerous advantages over conventional electrolytes because they are stable, non-flammable, and often much more environmentally friendly.

To explore the exciting potential offered by ionic liquids for emerging electrochemical technologies the authors designed a new set of highly efficient detergent-like ionic liquid electrolytes and explained how they work at electrode surfaces.

Understanding how they operate will help design even more efficient devices for storing electrical energy.

Professor Julian Eastoe, from the University of Bristol's School of Chemistry, is a co-author of the study. He said: "To make this discovery required a team of scientists with a very diverse skill set, spanning chemical synthesis, advanced structural, microscopy and electrical techniques as well as computational methods.

"This work demonstrates the power of scientific research 'without borders', the groups from different nations contributed their own expertise to make 'the whole greater than the sum of parts'."

Co-author, Xianwen Mao, from the Massachusetts Institute of Technology (MIT), added: "We engineered a new class of ionic liquids that can store energy more efficiently.

"These detergent-like ionic liquids can self-assemble into sandwich-like bilayer structures on electrode surfaces. And that is very reason why they give better energy storage performance."

Typically, for electrolytes in contact with a charged electrode, the distribution of ions is dominated by electrostatic Coulombic interactions.

However, this distribution can be controlled by making the ionic liquids soap-like, or amphiphilic, so that the molecules now have separate polar and non-polar domains, exactly like common detergents.

These soap-like electrolytes then spontaneously form bilayer structures on the electrode surfaces, leading to much improved energy storage capabilities. The researchers found that temperature and applied voltage also affect the energy storage performance.

This new class of electrolytes may be suitable for challenging operations, such as oil drilling and space exploration, but they may also pave the way to new and improved supercapacitors in hybrid cars.

These devices are essential components in modern hybrid cars and can outperform batteries in terms of higher power and better efficiency.

This is particularly the case during regenerative braking where mechanical work is turned into electrical energy, which can be stored quickly in supercapacitors ready to be released.

This reduces energy consumption and is much more environmentally friendly. More importantly, using the new electrolytes such as developed in this study, future supercapacitors may even be able to store more energy than batteries, potentially replacing batteries in applications such as electrical vehicles, personal electronics, and grid-level energy storage facilities.

Engineers at the University of California San Diego have developed the thinnest optical device in the world--a waveguide that is three layers of atoms thin.

The work is a proof of concept for scaling down optical devices to sizes that are orders of magnitude smaller than today's devices. It could lead to the development of higher density, higher capacity photonic chips. Researchers published their findings Aug. 12 in Nature Nanotechnology.

"Fundamentally, we demonstrate the ultimate limit for how thin an optical waveguide can be built," said senior author Ertugrul Cubukcu, a professor of nanoengineering and electrical engineering at UC San Diego.

The new waveguide measures about six angstroms thin--that is more than 10,000 times thinner than a typical optical fiber and about 500 times thinner than on-chip optical waveguides in integrated photonic circuits.

The waveguide consists of a tungsten disulfide monolayer (made up of one layer of tungsten atoms sandwiched between two layers of sulfur atoms) suspended on a silicon frame. The monolayer is also patterned with an array of nanosized holes forming a photonic crystal.

What's special about this monolayer crystal is that it supports electron-hole pairs, known as excitons, at room temperature. These excitons generate a strong optical response, giving the crystal a refractive index that is about four times greater than that of air, which surrounds its surfaces. By comparison, another material with the same thickness would not have as high of a refractive index. When light is sent through the crystal, it is trapped inside and guided along the plane by total internal reflection. This is the basic mechanism for how an optical waveguide works.

Another special feature is that the waveguide channels light in the visible spectrum. "This is challenging to do in a material this thin," Cubukcu said. "Waveguiding has previously been demonstrated with graphene, which is also atomically thin, but at infrared wavelengths. We've demonstrated for the first time waveguiding in the visible region."

Nanosized holes etched into the crystal allow some light to scatter perpendicular to the plane so that it can be observed and probed. This array of holes produces a periodic structure that makes the crystal double as a resonator as well.

"This also makes it the thinnest optical resonator for visible light ever to be demonstrated experimentally," said first author Xingwang Zhang, who worked on this project as a postdoctoral researcher in Cubukcu's lab at UC San Diego. "This system does not only resonantly enhance the light-matter interaction, but also serves as a second-order grating coupler to couple the light into the optical waveguide."

Researchers used advanced micro- and nanofabrication techniques to create the waveguide. Creating the structure was particularly challenging, said Chawina De-Eknamkul, a nanoengineering PhD student at UC San Diego and a co-author of the study. "The material is atomically thin, so we had to devise a process to suspend it on a silicon frame and pattern it precisely without breaking it," she said.

The process starts with a thin silicon nitride membrane supported by a silicon frame. This is the substrate upon which the waveguide is built. An array of nanosized holes is patterned into the membrane to create a template. Next, a monolayer of tungsten disulfide crystal is stamped onto the membrane. Ions are then sent through the membrane to etch the same pattern of holes into the crystal. In the last step, the silicon nitride membrane is gently etched away, leaving the crystal suspended on the silicon frame. The result is an optical waveguide in which the core consists of a monolayer tungsten disulfide photonic crystal surrounded by a material (air) with a lower refractive index.

Moving forward, the team will continue to explore the fundamental properties and physics pertaining to the waveguide.

Magdeburg, August 8th 2019 - Democracy, environmental protection, peace - the great issues of our time are collective goods that can only happen if many people make a voluntary contribution. However, the theory of collective action, which has been held for over 50 years, states that there is no incentive for individuals in large groups to participate in the provision of work for public benefit. Frankly speaking, individuals lack motivation because their contributions stand in no relation to the very small influence they can exert. With the largest laboratory experiment in economic research to date, a group of German experimental economists have now shaken this theory to the core and made an astonishing discovery. With considerable implications for the way participation is handled politically, our commitment is by no means only dependent on the influence we have. What is far more important is whether we really know what we are striving for.

World issues such as climate protection and the right to personal freedoms benefit all, regardless of whether everyone contributes to them or not. It is therefore a perfectly rational strategy for the individual solely to be a beneficiary. Conversely, this means that the state of affairs regarding issues impacting everyone is not in a good shape. This does indeed seem to correspond to our everyday experience: Why should I give up my car if millions of others don't?

Flight passenger numbers are rising at the same rate as environmental awareness -
a contradiction?

Since Mancur Olson's book "The Logic of Collective Action", published in 1965, science has invoked the theory that large groups are unable to make decisions benefitting the greater good. According to this, these groups fail on the grounds of a fundamental contradiction. Although all members of the group would be better off if the outcomes were made available, the incentive for individuals to actually contribute to them is infinitely small - their very minimal influence is offset by costs that are perceived to be too high. For example, it is inconvenient for the individual homeowner to turn down the heating and dress warmer to reduce CO2 emissions. Yet the impact of this measure on climate change is practically undetectable. The realization that less air traffic would contribute to more climate protection does not prevent people from using airplanes - passenger numbers are rising at the same rate as environmental awareness.

The visibility of the benefits of cooperation is what counts

In the largest laboratory experiment ever carried out in experimental economic research, financed by the German Research Foundation (DFG), a group of German experimental economists, led by Joachim Weimann from Magdeburg, has now tested Olson's theory under laboratory conditions. By linking four laboratories via the Internet, Weimann and his colleagues, Jeannette Brosig-Koch from the University of Duisburg-Essen, Heike Henning-Schmidt from the University of Bonn, Claudia Keser from Göttingen, and Timo Heinrich from Durham University, were able to bring large groups together in a virtual environment under laboratory conditions. With more than 5,000 subjects, they came to a surprising conclusion: in both large groups and small, controlled ones, members were willing to engage. The researchers did not observe the effect described by Olson which said that individuals in large groups were not able to cooperate on a mutually-beneficial task if their impact on issues is negligible.

Instead, it turns out that cooperative decision making in large groups depends on something that had previously not been considered in research. The absolute value of the contribution (which can be very small) is in fact less important than the relationship between this contribution and the significance of the

individual in a group. The researchers interpret this as an indicator of the visibility (salience) of the mutual advantage generated by cooperative behavior: "My own cooperation helps others, and the cooperation of others benefits me."

The danger and opportunity involved in solving large tasks

This, however, opens up a completely new approach in terms of research on issues related to the public good. If it can be confirmed that it is indeed the visibility of the benefits of cooperation that is crucial for large groups to take collective action, new questions of considerable practical and political importance will arise. This would mean, for example, that democratic systems would be put at risk if citizens were no longer sufficiently aware of the mutual benefits for everyone arising from participation in political life. Furthermore, it would mean that the solution to environmental problems depends crucially on whether the benefits of environmentally-friendly behavior are sufficiently well known and the public is aware of them. Moreover, it would suggest that issues surrounding the public good therefore arise first and foremost when the benefits of their solution are not sufficiently visible.

One third of people are cooperative, but voluntary action alone is not enough

This large-scale experimental project has also shown, however, that even under the ideal conditions of a laboratory, relying solely on the voluntary cooperation of individuals only leads to a partial solution for issues that benefit the greater good. Nevertheless, a third of the participants were willing to cooperate if there was sufficient salience. And this is where the opportunity lies: "Thirty percent support - in democratic systems, this is an indispensable basis for rational, collective (i.e. political) decisions," says Joachim Weimann.

A team from the Institut National de la Recherche Scientifique (INRS) has made a scientific breakthrough regarding the virulence strategy employed by the Leishmania parasite to infect cells of the immune system. This microorganism is responsible for Leishmaniasis, a chronic parasitic disease that affects more than 12 million people worldwide.

The Leishmania parasite was already known to conquer its host--human or animal--by sabotaging the macrophage defence system, macrophages being a type of white blood cell active in the body's frontline immune response. The mechanics of Leishmania virulence strategies, however, remained unclear.

INRS professor Albert Descoteaux and his team, in collaboration with researchers from McGill University, Université de Montréal, and Tohoku University, have discovered that Leishmania exploits an intracellular transport mechanism already present in macrophages to spread its virulence factors. The results of the team's research were published in the journal PLOS Pathogens.

"It's like there's a train travelling among the different intracellular compartments that the parasite boards to deliver its virulence factors inside the infected cell," says Professor Descoteaux, the study's lead author. "Our study sheds new light on the pathogenesis of infection."

Explanations

Leishmania is transmitted to the mammalian host through a bite from an infected phlebotomine sand fly. The parasite has two key molecules on its surface that allow it to infect the host cell's interior: the GP63 metalloprotease and lipophosphoglycan (LPG). These are known as virulence factors.

Upon infecting the macrophage, Leishmania enters a parasitophorous vacuole that it hijacks with the help of virulence factors. This vacuole acts as a sort of "protective bubble" against the host cell's immune defences. Leishmania creates a compartment in the host cell where it can replicate.

Researchers wanted to understand how the parasite's molecules reach their targets inside the infected cells and what mechanisms they employed.

"Most research teams study the impacts of virulence factors, but until now no one understood how Leishmania was able transfer virulence factors from the vacuole to the cytoplasm of the infected cell. That's what we've just shown with our work," says the study's first author, Guillermo Arango Duque, who recently received his PhD in virology and immunology supervised by Professor Descoteaux.

"We discovered that Leishmania co-opts the macrophage's membrane fusion machinery to export virulence factors out of the vacuole," he adds.

Interconnected cellular compartments

Since the parasite successfully transfers its virulence factors (GP63 and LPG molecules) to the other side of the vacuole's membrane, it was necessary to determine what other compartment of the infected host cell contained these factors.

The researchers observed that most of the virulence factors were found in a compartment called the endoplasmic reticulum (ER). This compartment takes up the most space in the host cell and is connected with all other intracellular compartments. They concluded that this facilitated the spread of virulence factors within the cell.

They then used the latest genetic technology to identify the molecules involved in intracellular trafficking that are needed to spread Leishmania virulence factors in the infected host cell. The team found that by decreasing the expression of two host cell molecules, sec22b and syntaxin-5, that are responsible for regulating intracellular traffic in the ER, they could block the spread of virulence factors in the infected cell and interfere with their actions.

"To fully understand what enables the compartment where Leishmania replicates to connect with other compartments of the infected host cell is a major step forward," Professor Descoteaux says. "This pathway could also be exploited by other intracellular microorganisms such as Mycobacterium tuberculosis, which is the agent of tuberculosis, or Legionella pneumophila, which causes Legionnaires' disease."

The next step will be to find out to what extent, by manipulating or blocking this pathway over the long term, researchers could interfere with parasite replication without significantly altering how the cell functions.

One quarter of the world's tropical land could disappear by the end of the century unless meat and dairy consumption falls, researchers have warned.

If the global demand for animal products continues to grow, large swathes of natural land will vanish potentially leading to widespread loss of species and their habitats.

Some nine per cent of natural land - 95 per cent of which is in the tropics - could go within 80 years unless global dietary habits change, the scientists say.

Researchers at the University of Edinburgh and Karlsruhe Institute of Technology studied the impact of consumption trends on biodiverse regions - areas that have a wealth of mammals, birds, amphibians and plant life.

They found that rapid increases in meat and milk production result in sharp rises in land clearing in tropical regions that harbour high levels of biodiversity.

As incomes increase across the globe, consumption has shifted from staples such as starchy roots and pulses to meat, milk, and refined sugars.

Meat and dairy production is associated with higher land and water use and higher greenhouse gas emissions than any other foods.

By replacing animal products with plant-based alternatives, they predict that the global demand for agricultural land could be reduced by 11 per cent.

Researchers also found that industrial feed systems reduce agricultural expansion but may increase environmental degradation due to agricultural pollutants such as fertiliser.

The study comes after the Intergovernmental Panel on Climate Change last week published a special report that identified reducing meat consumption as an important focus for climate change mitigation.

Lead author Dr Roslyn Henry, said, "Reducing meat and dairy consumption will have positive effects on greenhouse gas emissions and human health. It will also help biodiversity, which must be conserved to ensure the world's growing population is fed. Changing our diets will lead to a more sustainable future and complement food security goals while addressing global food inequalities."

Mosquitoes can harbor thousands of malaria-causing parasites in their bodies, yet while slurping blood from a victim, they transmit just a tiny fraction of them. In an effort to define precisely the location of the parasite bottleneck, Johns Hopkins Medicine scientists say they have discovered that the parasites are stopped by a roadblock along the escape route in the insect's spit glands, a barrier that could potentially serve as a novel target for preventing or reducing malarial infection.

"Our findings add substantial detail to the role of mosquito salivary glands as the gateway organs for diseases spread by these insects," says Deborah Andrew, M.S., Ph.D., professor of cell biology at the Johns Hopkins University School of Medicine. "By enhancing transmission barriers that naturally exist in mosquitos, we potentially can block the spread of malaria and other deadly mosquito-borne diseases, like Zika fever."

An estimated 220 million people worldwide, mostly in tropical and subtropical regions, have malaria, and more than 400,000 die of the parasite infection each year, according to the World Health Organization. Marked by disabling fever, chills, fatigue and sweating, the disease can be treated with drugs and prevented with mosquito eradication programs, but the high costs of drugs and eradication methods consistently hamper efforts to reduce malaria's prevalence. Other mosquito-borne diseases, including dengue fever, strike scores of millions more.

A description of the research is published in the Aug. 6 issue of the journal mBio.

Malaria parasites are dependent on female Anopheles mosquitoes to spread in a complex life cycle that begins when mosquitos eat male and female parasite sex cells during a blood meal from an infected animal host. The cells wind up in the mosquito's gut, where they fuse to form fertilized eggs that then squeeze through the gut's lining and become encased in cysts in the insect's body cavity. In these cysts, the parasites begin a reproductive frenzy, making more and more copies of themselves. When the cysts finally burst, the parasites raid the salivary gland by the hordes, ready to be squirted out when the mosquito takes its next blood meal. But scientists have long observed that most of them never make it out of the mosquito.

"Even though thousands of parasites invade the salivary gland, less than a 10th of them are transmitted during a mosquito bite," says Michael Wells, Ph.D., postdoctoral researcher in Andrew's laboratory and the study's lead author. "So, we knew that the salivary gland is blocking the parasites from getting out, but we didn't know exactly how."

The Anopheles mosquito's salivary gland is made up of three lobes of saliva-producing cells. The lobes are encased in a protective sheet called the basement membrane, and in each lobe are long ducts that extend into the insect's mouth. For release, the parasites must first go through the basement membrane, penetrate a layer of salivary cells and then swim across a space called the secretory cavity to reach the salivary duct.

To study how the salivary gland might obstruct malaria transmission, the researchers first let Anopheles mosquitoes feed on rodent blood enriched with malaria parasites. Since the mosquitoes decided how much they ate, each one consumed a different quantity of parasites. This offered the researchers data for different quantities of parasitic infection from hundreds of mosquito salivary glands.

The researchers then systematically mapped out the parasites' location by dissecting salivary glands from these mosquitos and looking for the parasites under high-powered microscopes. They found that most parasites were either inside the basement membrane or in the secretory cavity. But only a few parasites were in the salivary ducts.

"The parasites seem to have no trouble getting into the salivary glands," says Wells. "So, this told us that the obstruction happens later, when parasites are trying to get to the salivary duct."

Next, the researchers zoomed in on the cell layers in each lobe of the salivary gland. They found that most parasites appeared unable to leave the secretory cavity and were congregating at a fibrous, sturdy wall made of a substance called chitin that forms around the salivary ducts.

Some parasites, however, were able to tunnel through the chitin wall and reach the salivary duct, but like traffic bottlenecks, the narrow opening they burrowed into allowed only a few parasites to pass through. Wells says the lucky parasites that make it through the tough duct wall are likely the ones that are released during a bite.

If the chitin wall around salivary ducts can be fortified, infections may be thwarted. "Our study is a first step in better understanding how salivary glands in malaria-carrying mosquitoes limit the transmission of disease parasites," says Andrew. "In the future, we hope this information will advance strategies to limit transmission and uncover how other insects have evolved ways to affect disease transmission."

It's a comment we often hear in response to stories of child neglect: that parenting should require a licence.

Researcher Dr Frank Ainsworth from James Cook University in Australia says that while the suggestion is based on concern for children, it is fraught with problems.

Dr Ainsworth, an adjunct senior principal research fellow with JCU's social work department, reviewed international studies on parental licensing and Australian statistics on children in care.

"Parental licensing is the idea that parenting competence should be demonstrated prior to adults achieving full parental rights. It's a long-standing idea among a host of academic philosophers, political scientists and others interested in children's rights," he said.

His review showed that while the intent was good, the problems that would come with a parental licensing system made it unworkable and open to abuse.

"The biggest problem is the question of parental licensing being a concealed policy of eugenics," he said.

Dr Ainsworth said parental licensing included the notion that while pregnant women would be allowed to give birth, if they were not licensed to raise children the baby would be removed and put up for adoption.

He said the denial of parenting rights would almost certainly fall more heavily on people with higher rates of socio-economic disadvantage.

"You have to remember that denying a parental licence is not the same as denying any other kind of licence, such as a driving licence. There are no alternatives to parenting a child. Parenting denied is final," he said.

Dr Ainsworth said there is also the question of how a testing system would deal with potential parents with an intellectual disability, those with a physical disability, those who are illiterate and migrants who cannot speak English.

"Disadvantaged sections of the community, and their supporters, would be loud in their opposition to any form of parental licensing," he said.

Dr Ainsworth said his study of adoption statistics indicated that even if such a scheme received political support, there may not be enough people wanting to adopt.

"On the evidence and discussion I've reviewed, it's hard to see parental licensing serving anyone well, especially the children it would be intended to help," he said.