Culture

If it's thoughts of zombies that keep you awake at night, you shouldn't be worried about zombie humans; it's the carpenter ants (Camponotus castaneus) that should concern you most. When infected by a specialised fungus (Ophiocordyceps unilateralis sensu lato), the hapless ants are unable to resist its potent power. Losing free will, the unfortunate victims locate tall pieces of vegetation, marching to a high point before the fungal infection forces them to clamp their mandibles - jaws - tightly onto a leaf vein or twig. There, the ill-fated host expires, only to be consumed from within by its evil fungal lodger, ready to scatter its spores below in the hope of infecting the next unsuspecting victim. Yet, despite the insects' loss of control, Colleen Mangold from Pennsylvania State University, USA, explains that the fungus does not attack their brains directly: 'the mandibular muscles ... of infected ants are extensively colonised by the fungus', she says. Wondering how the fungus exerts control over the ants' powerful jaw muscles, Mangold and PI David Hughes decided to take a closer look inside the muscle itself. They have discovered that the fungus invades the mandibular muscles, breaks open the membrane covering the muscle fibres and forces the muscle to contract so forcefully that it wrecks the minute muscle filaments that slide past each other. The team publishes the discovery in Journal of Experimental Biology at http://jeb.biologists.org.

'The most difficult aspect of the study was the infections', says Mangold, explaining that the fungus cannot take hold inside ant nests; the insects must be roaming free to be susceptible. Even then, the fungus only thrives in the humidity of Brazil or South Carolina, so Mangold, Melissa Ishler and Rachel Loreto had to recreate a warm humid environment in the lab in order to collect the infectious spores from diseased individuals. The team also had to figure out the correct dose of spores to ensure that the ants could not defeat the fungus before it took effect and forced them to lock their jaws tightly onto a piece of foliage.

Swiftly freezing the dying insects and removing their jaw muscles before preserving them and scrutinising the structures in an electron microscope, Missy Hazen and Mangold could see that fungus filaments had penetrated the muscle. However, when the team investigated the structures where nerve signals enter the muscle, they were unaffected; the fungus had not disabled the nervous system to weld the jaws in place. Instead, it looked as if the fungus had caused the muscle to contract so forcefully that the filaments in the muscle fibres - which slide past each other when the muscle contracts - were damaged and swollen. In addition, the fungus had broken the membrane covering the muscle fibres, leaving the fibres exposed and potentially vulnerable to toxins released by the invader. They also noticed tiny bead structures (vesicles) attached to the fungus filaments, which they suspect could be part of the ants' attempts to fight back at the lethal infection, or be packed with fungal toxins that could send the muscle into spasm, causing it to over-contract, clamping the jaws of the zombified ant in place.

However, Mangold adds that there is still more to learn about the fungus's influence on its innocent ant hosts. 'The next steps we want to take include isolating those vesicles and determining whether they are coming from the fungus or the host', she says; and she is keen to find out exactly what is packaged within. In the meantime, I hope your dreams aren't too haunted by the prospect of hordes of zombie ants scrambling to their final destiny.

Around one in 20 (6%) of patients are affected by preventable harm in medical care, of which around 12% causes permanent disability or death, finds a study published by The BMJ today.

Most preventable harm relates to drug incidents and invasive procedures and it is more common in surgical and intensive care units than in general hospitals.

Preventable harm also accounts for an estimated $9.3 billion (£7.3bn; €8.2bn) excess charges in the US. Similarly, the financial cost from only six selected types of preventable patient harms in English hospitals is equivalent to over 2000 salaried general practitioners or over 3500 hospital nurses each year.

As such, the researchers say strategies targeting preventable patient harm could lead to major improvements in medical care and considerable cost savings for healthcare systems across the globe.

Preventable patient harm is a serious problem across medical care settings globally, and early detection and prevention is an international policy priority. Several previous reviews have examined overall patient harm across different settings, but none have focused on preventable patient harm.

So a team of researchers led by Maria Panagioti from the NIHR Greater Manchester Patient Safety Translational Research Centre set out to measure the prevalence of preventable patient harm across a range of medical settings, including hospitals and in primary care. They also examined the severity and most common types of preventable patient harm.

Their findings are based on data from 70 observational studies involving 337,025 mostly adult patients. Of these, 28,150 experienced harmful incidents and 15,419 experienced preventable harmful incidents.

Around 12% of the preventable harm was severe (causing prolonged, permanent disability or death), while incidents relating to drugs and other treatments accounted for almost half (49%) of preventable harm

Compared with general hospitals, preventable harm was more common in patients treated in surgical and intensive care units, and was lowest in obstetric units.

Despite the unique focus on preventable patient harm and several method strengths, this review has some limitations, say the authors. For example, variations in study design and quality of documentation used for detecting preventable patient harm may have led to differences in prevalence estimates.

Nevertheless, they say their findings "affirm that preventable patient harm is a serious problem across medical care settings" and "priority areas are the mitigation of major sources of preventable patient harm (such as drug incidents) and greater focus on advanced medical specialties."

It is equally imperative to build evidence across specialties such as primary care and psychiatry, vulnerable patient groups, and developing countries, they add. "Improving the assessment and reporting standards of preventability in future studies is critical for reducing patient harm in medical care settings," they conclude.

This view is supported by experts at the London School of Economics and Harvard Medical School in a linked editorial.

They say this study "serves as a reminder of the extent to which medical harm is prevalent across health systems, and, importantly, draws attention to how much is potentially preventable."

Moving forward, they say "efforts need to be focused on improving the ability to measure preventable harm. This includes fostering a culture that allows for more systematic capturing of near misses, identifying harm across multiple care settings and countries, and empowering patients to help ensure a safe and effective health system."

With obesity now affecting almost a third (29%) of the population in England, and expected to rise to 35% by 2030, should we now recognise it as a disease? Experts debate the issue in The BMJ today.

Obesity, in which excess body fat has accumulated to such an extent that health may be adversely affected, meets the dictionary definition of disease, argue Professor John Wilding at the University of Liverpool and Vicky Mooney, representing the European Coalition for People living with Obesity (ECPO).

They point out that more than 200 genes influence weight, and most of these are expressed in the brain or in adipose tissue. "Thus body weight, fat distribution, and risk of complications are strongly influenced by biology - it is not an individual's fault if they develop obesity."

They argue that the recent rapid increase in obesity is not due to genetics but to an altered environment (food availability and cost, physical environment, and social factors).

Yet the widespread view is that obesity is self inflicted and that it is entirely the individual's responsibility to do something about it, while healthcare professionals seem ill informed on the complexity of obesity and what patients with obesity want.

Recognising obesity as a chronic disease with severe complications rather than a lifestyle choice "should help reduce the stigma and discrimination experienced by many people with obesity," they add.

They disagree that labelling a high proportion of the population as having a disease removes personal responsibility or may overwhelm health services, pointing out that other common diseases, such as high blood pressure and diabetes, require people to take action to manage their condition.

They suggest that most people with obesity will eventually develop complications, and those who do not could be considered as not having disease. "But unless we accept that obesity is a disease, we are not going to be able to curb the epidemic," they conclude.

But Dr Richard Pile, a GP with a special interest in cardiology and Clinical Lead for Prevention for Herts Valleys Clinical Commissioning Group, argues that adopting this approach "could actually result in worse outcomes for individuals and society."

He believes that the dictionary definition of disease "is so vague that we can classify almost anything as a disease" and says the question is not whether we can, but whether we should, and to what end.

If labelling obesity as a disease was harmless then it wouldn't really matter, he writes. But labelling obesity as a disease "risks reducing autonomy, disempowering and robbing people of the intrinsic motivation that is such an important enabler of change."

There is an important difference psychologically between having a risk factor that you have some responsibility for and control over and having a disease that someone else is responsible for treating, he says.

What's more, making obesity a disease "may not benefit patients, but it will benefit healthcare providers and the pharmaceutical industry when health insurance and clinical guidelines promote treatment with drugs and surgery," he warns.

While self determination is key in enabling change, "we should acknowledge that the origins of obesity for most people are social, and so too is the solution," he adds. "If people meet, shop, cook, eat, and engage in activities together the end result will be improved wellbeing and reducing obesity will be a consequential beneficial side effect."

Classifying obesity as a disease is neither essential nor beneficial. It's much more complicated than that, he concludes.

A University of Massachusetts Amherst environmental epidemiologist studying the presence of PFAS compounds in new mothers and their babies found that women with gestational diabetes had a "significantly higher" rate of transferring the synthetic chemicals to their fetus.

The newly published study in Environment International is among the largest to date in terms of the number of per- and polyfluoroalkyl substances (PFASs) examined - 17. Those particular compounds are among the PFAS chemicals associated with growing health concerns, including cancer risk, hormone interference, immune system suppression and developmental disruptions in infants and children.

Since the 1950s, PFAS compounds have been used worldwide in common household and industry goods, including nonstick cookware, water- and stain-resistant materials and food packaging. These "forever chemicals," so called because they do not break down in the environment, are also used in aqueous firefighting foams at military training sites and can infiltrate drinking water, which has become a major source of exposure in specific communities, including in Massachusetts.

"The contamination is all over the world," says Youssef Oulhote, assistant professor of biostatistics and epidemiology at UMass Amherst and the study's corresponding author. "We find them even in polar bears."

Blood and umbilical cord samples from 151 mother-newborn pairs in the Faroe Islands were examined by Oulhote and public health colleagues at Sorbonne University in Paris, the University of Southern Denmark, the Faroese Hospital System and Harvard University, where Oulhote began his research into the health effects of chemicals.

The Faroe Islands are located off the coast of Northern Europe, halfway between Norway and Iceland. The local population, which traditionally eats a lot of whale, is genetically and socioeconomically homogeneous, minimizing "confounding factors" in the research. "Most importantly, they consume whale, which is high in the food chain, so it accumulates many of the contaminants," Oulhote explains.

The study was the largest to date to model both the ratios of transplacental transfer and the patterns of transfer in the blood and plasma of multiple PFAS with different physical and chemical properties and different maternal and newborn characteristics.

While previous research has shown that PFAS compounds cross the placental barrier and reach the fetus, this study was the first to note the effects of gestational diabetes. "It's one of the most consistent results we got," Oulhote says. "There was up to a 50 percent greater transfer on average" in mothers with gestational diabetes. "We hypothesized that diabetes mellitus alters the kinetic disposition and metabolism of these chemicals. We know this has been shown to happen with some drugs and some nutrients in previous studies."

The researchers found that the transfer ratio depended on the physical and chemical structure of the compounds. Some PFAS compounds have been phased out since 2002 due to concerns about their toxicity. Newer PFAS compounds have shorter carbon chains and are assumed to be less toxic and accumulate less.

Infants who develop eczema are more likely to develop food allergies, hay fever and asthma as they grow older, a progression known as the atopic march. Donald Leung, MD, PhD, head of Pediatric Allergy & Clinical Immunology at National Jewish Health, has identified itching and dry cracked skin of eczema patients as a significant promoter of the atopic march. Moisturizers, especially early in a child's life, may help prevent eczema, food allergies and other allergic diseases.

"When food particles are introduced through the skin rather than the digestive system, they are much more likely to cause allergies," said Dr. Leung. "Cracks in the skin of those with eczema often set off a chain of allergic diseases that develop over several years."

Seventeen-year-old Ava Segur experienced the atopic march first hand. It started with eczema when she was just six weeks old. Her mother, Stephanie, says they were trying to get her skin inflammation under control, when they were suddenly confronted with another problem. "She had hives all over her arms and neck," she said. "So we took her to the hospital and found out she is allergic to peanuts, pine nuts and shellfish." A few years later, Ava developed exercise-induced asthma.

Ava has participated in numerous clinical trials seeking better treatments for eczema and a better understanding of the atopic march. "If we can find a solution that will work to stop this before it starts, it will be very rewarding to know that I was able to be a part of that," said Ava.

"Restoring the skin barrier as soon as eczema develops is the best way to stop the atopic march in its tracks and prevent allergic diseases from developing," said Dr. Leung.

The skin forms an important barrier, keeping moisture in and external allergens or microbes out. Research by Dr. Leung has shown that patients with eczema lack important proteins and lipids in the outer layers of their skin. As a result of eczema patients' defective skin barrier, water escapes from the skin, drying it out and leading to cracking and itching. Cracked, itchy skin is a hallmark of eczema.

Scratching the dry, itchy skin of eczema patients can further damage the skin barrier and activate the immune system. Increasing evidence compiled by Dr. Leung and others indicates that food particles entering the body through cracks in the skin can trigger an allergic response that leads to food allergy. Once that allergic response has been triggered, the immune system is primed to develop not only eczema and food allergies, but also hay fever and asthma.

To do this, experts recommend what they call "soak and seal," which involves thoroughly moisturizing the skin in a warm bath, then trapping the moisture in with a moisturizing ointment. It's a method Kriston Kline says helped her 19-month-old son's skin begin to heal within a week.

"It provided him with immediate relief, and each time we do a soak-and-seal treatment, his skin looks so much better," said Kline. "Not only is this making him more comfortable now, but if it can help protect him from allergies and asthma, that is a huge benefit for his future."

Dr. Leung believes that careful care of a baby's skin right from birth could prevent eczema and other allergic diseases. A baby's skin is particularly susceptible to drying out when it first emerges from the warm, watery environment of the womb into the dry air of the outside world. A few small studies have suggested that regular treatment with skin moisturizers can help reduce an infant's chances of developing eczema and the other diseases in the atopic march. Dr. Leung is currently working to confirm those studies and identify the ideal moisturizer components to prevent eczema and the other diseases of the atopic march.

Marine protected areas, or MPAS, are an increasingly common way of protecting marine ecosystems by prohibiting fishing in specific locations. However, many people remain skeptical that MPAs actually benefit fish populations, and there has not yet been a way to demonstrate whether or not they are effective. Until now.

A study published July 17 in the Journal of Applied Ecology is the first description of how to use data collected before and after a protected area is implemented to measure its effectiveness. Data collected beforehand can help predict how much fish populations are expected to increase. Then scientists can compare it to data collected after the MPA is in place to help determine whether adjustments are needed, such as changing the size or enforcement levels of an MPA.

SAFEGUARDING CALIFORNIA'S MARINE LIFE

California's Marine Life Protection Act of 1999 was created to safeguard some of the state's most treasured resources -- its coast and ocean. It mandated that such areas be managed adaptively, with the ability to be changed if needed to meet the goals of preserving the diversity and abundance of marine life off the California coast. But, since its implementation, there has not been a way to assess whether or not the state's MPAs are effective in meeting those goals.

"California has the second largest marine protected area network in the world -- the first is in Australia with the Great Barrier Reef -- and the rest of the world looks at California as an example of what can be done," said lead author Kerry Nickols, who began the work while a postdoctoral student at UC Davis and is now at California State University, Northridge.

Such areas are important havens for marine populations facing multiple threats, including climate change, overfishing and habitat degradation. In a sense, MPAs provide a "fence" around a healthy marine environment to preserve what's inside, Nickols said.

"We have developed a method for managing these MPAs that properly quantifies whether they are benefiting populations in the anticipated way," said co-author Louis Botsford, a professor emeritus at the UC Davis Department of Wildlife, Fish and Conservation Biology. "It demonstrates the possibility of transparently verifying that MPAs work."

Baylor College of Medicine researchers, in collaboration with the University of California, Los Angeles and Second Sight Medical Products (Los Angeles, Calif.) are using a visual cortical prosthesis to help bring sight to the blind. The study is in the early phases but participants are able to see points of light on a computer screen using a device called Orion. To put it simply, researchers are bypassing broken optical nerves that don't work and inputting visual information seen by a camera, worn on a pair of glasses, directly into the Orion device implanted in the brain. Benjamin Spencer talks about his experience taking part in the study and Dr. Daniel Yoshor explains the science that goes into bringing sight to the blind.

New Marketing Science Study Key Takeaways:

Research shows once recreational marijuana is legalized, the number of online searches for tobacco increase by 8%, while searches for alcohol drop by 11%.

The findings could have an implication on sales for the alcohol and tobacco industries.

The passing of recreational cannabis increases online searches for cannabis done by adults by 17%, but not by youth.

CATONSVILLE, MD, July 17, 2019 - The recent wave of recreational cannabis legalization across the U.S. could generate $22 billion in sales per year, but not everyone is happy about it. New research to be published in an upcoming edition of the INFORMS journal Marketing Science, titled, “Asymmetric Effects of Recreational Cannabis Legalization,” shows the alcohol industry could be impacted when the substance is legalized.

"It appears the alcohol industry has valid reason to be concerned about legal marijuana and may need creative strategies to avoid market decline if it passes," said Pengyuan Wang, an assistant professor in the Terry College of Business at the University of Georgia.

The study shows online searches for alcohol saw a drop of nearly 11%, but tobacco products were searched online nearly 8% more often.

The U.S. alcohol and tobacco industries are worth a combined $300 billion. They are typically avid opponents of marijuana legalization legislation, but this research suggests, "tobacco companies may need to reexamine their presumption, and that anti-cannabis legalization is not to the best of their interest," said Wang.

The research by Wang and co-author Guiyang Xiong of Syracuse University looked at anonymous data from 28 million online searches and 120 million ad impressions from a leading U.S.-based web portal from January 2014 to April 2017.

The study also found the legalization of recreational marijuana increases online searches by adults by 17%. There is actually a decrease in searches done by those age 19 years and younger after the substance is legalized.

"Contrary to widely held public concern after recreational cannabis is legalized, teenagers appear to lose interest, rather than gain interest," added Wang. "Policymakers only concerned with an uptick in teen users, may want to rethink their stance."

A quarter of women who have serious maternal complications during childbirth also have premature births, posing a "dual burden" on families, finds research from NYU Rory Meyers College of Nursing, the University of California, San Francisco (UCSF) California Preterm Birth Initiative, and Stanford University.

The study, published online in The Journal of Maternal-Fetal & Neonatal Medicine and the first to focus specifically on "dual burden" births, shows that these complications occur in one of 270 births and are twice as likely to affect Black mothers.

"The situation of combined maternal and newborn complications is likely to be extremely stressful for families concerned for both the mother's and the infant's heath. However, healthcare providers may not fully recognize this, especially when maternal and newborn care are delivered by different specialists. There's not enough attention to the combined effect on the family," said Audrey Lyndon, PhD, RN, FAAN, professor of nursing and assistant dean for clinical research at NYU Rory Meyers College of Nursing, as well as the study's lead author.

Premature infants--those born at less than 37 weeks--experience a range of health issues, including problems with breathing, digestion, heart rate, and development. Mothers can also face serious to potentially life-threatening health issues during childbirth. These maternal complications--also known as severe maternal morbidity--include serious bleeding that requires a blood transfusion, blood clots, heart failure, emergency hysterectomies, and other serious problems. Research shows that severe maternal morbidity is rare but is also increasing nationally, with rates more than doubling from 2002 to 2014, and can have ongoing consequences for women and their families.

While prior studies have shown associations between premature birth and severe maternal morbidity, the prevalence of experiencing the "dual burden" of both has not been studied until now. Lyndon and her colleagues examined data from all California births from 2007 through 2012, a total of 3.1 million births. California keeps robust data on childbirth for its diverse population and accounts for approximately one in eight of all U.S. births.

The researchers found that the rates of preterm birth were 876 per 10,000 births, and the rates of severe maternal morbidity were 140 per 10,000 births. A quarter of the women with severe maternal morbidity, or one per 270 births, also had their babies prematurely. The majority of these "dual burden" births occurred in cases of preterm labor (61 percent) rather than births that needed to occur early for medical reasons (23 percent).

Several factors were associated with a higher risk of a "dual burden" birth, including cesarean birth, carrying multiples, smoking during pregnancy, being underweight, high blood pressure, and diabetes. The researchers also found that Black women were twice as likely to have a "dual burden" birth as White women when controlling for other factors.

"Racial disparities in health outcomes should be considered markers of exposure to racism, where poorer health reflects the exposure to chronic stress from discrimination and structural inequity, rather than race being a 'risk factor' for disease or poor health outcomes," said Lyndon. "Our study suggests that combined maternal and infant health challenges may result from exposure to racism for Black families and illustrates the transgenerational impact of such exposure."

Dual burden births have immediate and persistent physical, psychological, social, and financial consequences for women and their families. Furthermore, the experience may trigger post-traumatic stress disorder (PTSD) for women and their partners, leading to consequences including impaired parent-infant attachment, damaged partner relationships, and prolonged suffering and feelings of failure. These consequences could add to what may already have been racialized birth experiences for Black families, with Black women reporting disrespectful encounters when engaging reproductive health care services and Black preterm infants less likely to be referred for developmental follow-up.

"Imagine the deep trauma a family experiences when both the mother and newborn child are simultaneously fighting for their lives," said Laura Jelliffe-Pawlowski, PhD, MS, associate professor of epidemiology & biostatistics in UCSF School of Medicine, director of precision health and discovery with the UCSF California Preterm Birth Initiative, and the study's senior author. "This is the reality for 1,900 families in California, and it can have rippling effects across generations, particularly for Black families who are more likely to have a dual burden birth."

Given that mothers and newborns are cared for by different teams of specialists, the researchers point to the need for new models of care that explicitly coordinate infant and maternal health care teams and provide proactive support for the family's transition to home and long-term health

This study was supported by the UCSF California Preterm Birth Initiative, funded by Marc and Lynne Benioff. In addition to Lyndon and Jelliffe-Pawlowski, study authors include Rebecca Baer of the University of California, San Diego and the California Preterm Birth Initiative; Caryl Gay of UCSF School of Nursing and the California Preterm Birth Initiative; Alison M. El Ayadi of UCSF; and Henry Lee of Stanford University and the California Perinatal Quality Care Collaborative.

Two newly discovered organisms point to the existence of an ancient organism that resembled a tiny version of the lumbering, human-eating science fiction plants known as 'triffids,' according to research in Nature.

The microscopic protists Rhodelphis limneticus and Rhodelphis marinus are genetically 'sisters' to red algae, but couldn't be more different. Red algae are fleshy, large organisms with a simple genome that perform photosynthesis, just like plants. Rhodelphis are single-cell predators with a large, complex genome.

The two protists have a chloroplast, though it is not photosynthetic anymore, pointing to their close ties with plants in the distant past. They also have flagella, a whip-like structure which allows them to move and hunt for their dinner.

"Rhodelphis shows that there was a period of time when the ancestors of plants and algae probably absorbed sunlight to generate energy, while also swimming around eating things," says University of British Columbia (UBC) biologist Patrick Keeling, the senior researcher leading the study.

If we think of life as a big family, with algae and Rhodelphis as sisters, their ancient mother was more like a triffid than your standard plant. Triffids are the tall, mobile, carnivorous plants featured in John Wyndham's 1951 novel The Day of the Triffids.

This surprising evolutionary twist emphasizes the need for robust sampling in order to reconstruct a more complete picture of life.

"Most people don't look twice at organisms like this under a microscope, and getting them into culture may be hard work but it's the only way to really see the true diversity of life," says Denis Tikhonenkov, the microbiologist who first captured the tiny predators and splits his time between UBC and the Russian Academy of Science.

"There are gems in nature we haven't found, and sadly the importance of 'old-fashioned' exploration is being forgotten," Keeling says. "These new lineages are a great example -- making us realize we were previously seeing things backwards and now we recognize plants had ancestors we couldn't have imagined."

Keeling and Tikhonenkov worked on the project with the outstanding Russian Academy of Sciences protistologist Alexander Mylnikov, who died after a long illness shortly before the paper came to press.

A promising vaccine that clears an HIV-like virus from monkeys is closer to human testing after a new, weakened version of the vaccine has been shown to provide similar protection as its original version.

A pair of papers published July 17 in Science Translational Medicine describe how the vaccine - which uses a form of the common herpes virus cytomegalovirus, or CMV - was live-attenuated, or weakened so CMV couldn't spread as easily. The new version still managed to eliminate SIV, the monkey version of HIV, in 59 percent of vaccinated rhesus macaques. That result is similar to earlier findings involving the vaccine's original, non-attenuated version. The immunity generated by the attenuated vaccine was also long-lasting, as nine of 12 vaccinated monkeys could still fight off SIV infection three years later.

Having an attenuated version of the vaccine is key to being potentially able to use it in humans. No vaccines use non-attenuated live viruses due to safety concerns. Though humans are often infected with CMV without any trouble, the virus can wreak havoc on those with weakened immune systems such as people with organ transplants. It's also dangerous for pregnant women, as it can cause congenital defects such as hearing loss and microcephaly in babies.

"This research, using rhesus CMV, provides potentially important insights into the design of a human CMV-based HIV vaccine," said Klaus Früh, Ph.D., a corresponding author on one of the papers. "We significantly attenuated CMV and still got the same type of immune responses as with the wild version of this vaccine."

"These papers are important because they recapitulate the previously reported unique CMV vector efficacy with a genetically modified vector that is highly attenuated and therefore potentially safer for clinical use," said Louis Picker, M.D., a corresponding author on both papers. "In addition, this new work demonstrates most vaccinated rhesus macaques that are protected against SIV can also be protected against a second challenge years after initial vaccination. This is a level of durability that would be very important for a human HIV vaccine".

Picker and Früh are professors at OHSU's Vaccine & Gene Therapy Institute and affiliated faculty in the OHSU School of Medicine's department for molecular microbiology and immunology.

The CMV vaccine platform has been licensed by Vir Biotechnology, Inc., of San Francisco, which plans to lead a clinical trial with a human version of the CMV-based HIV vaccine. The same platform is also expected to be used for vaccines being developed to fight tuberculosis.

The community of viruses is staggeringly vast. Occupying every conceivable biological niche, from searing undersea vents to frigid tundra, these enigmatic invaders, hovering between inert matter and life, circumnavigate the globe in the hundreds of trillions. They are the most abundant life forms on earth.

Viruses are justly feared as ingenious pathogens, causing diseases in everything they invade, including virtually all bacteria, fungi, plants and animals. Recent advances in the field of virology, however, suggest that viruses play a more significant and complex role than previously appreciated, and may be essential to the functioning of diverse ecosystems.

We now know that humans contain roughly 100,000 pieces of viral DNA elements, which make up around 8 percent of our genome. Speculation on the role of these ancient viral fragments ranges from protection against disease to increasing the risk of cancer or other serious illnesses, though researchers acknowledge they have barely scratched the surface of this enigma.

A new review article appearing in the journal Nature Reviews Microbiology highlights the evolution and ecology of plant viruses. Arvind Varsani, a researcher at ASU's Biodesign Institute joins an international team to explore many details of viral dynamics. They describe the subtle interplay between three components of the viral infection process, the virus itself, the plant cell hosts infected by the virus and the vectors that act as go-betweens--an intricate system evolving over some 450 million years. All three elements are embedded within wider relations of the surrounding ecosystem.

Recent studies in the field of virology have shown that viruses are sometimes beneficial to the organisms they infect. "Prior to this people have always seen viruses as disease-causing entities," Varsani says. "This breaks all the dogmas of how we study viruses. We have a section where we review mutualism and symbiosis and also how some of the symbiotic relationships are being uncoupled."

Elusive wanderer

In 1892, Dmitry Ivanovsky, a Russian botanist, conducted a simple experiment that would have momentous implications for science and medicine. He collected sap from a diseased tobacco plant, fed the substance through very fine pores and showed that this filtered fluid could infect a healthy tobacco plant. The filtering ensured that whatever the disease-causing entity was, it was tinier than a bacterium. A Dutch plant specialist and microbiologist Martinus Beijerinck dubbed the mysterious pathogenic substance a virus, though its true form--invisible to light microscopy-- only appeared in 1931, with the invention of the electron microscope. A rod-shaped plant invader, known as tobacco mosaic virus, had revealed itself--the first virus on record. Since this time, thousands of distinct species have been identified, yet they represent a tiny fraction of the viral universe, most of which remains unexplored.

Indeed, even the question of what constitutes a virus has no single answer. Their sizes vary enormously, from a virus like Ebola, carrying a tiny handful of genes, to recently discovered giant viruses. Rivalling some bacteria in size, giant viruses can carry elements of the machinery required for translation, throwing their status as non-living entities into question.

"The way I look at viruses now is from a philosophical angle," Varsani says. "They are a dynamic entity and they have multiple lifestyles, ranging from basic, where the virus is fully reliant on the host for replication, to some cases where it's only partly reliant on the host." Because some viruses can evolve so rapidly, trading and acquiring new genetic elements, their genomes can become chimeric or even fragmented, making their proper classification a serious challenge for the field of virology.

From the standpoint of ecology, plant viruses are particularly important for a number of reasons. Plants make up over 80 percent of the biomass on earth, exerting a greater impact on the planet's diverse ecosystems than viruses infecting other kingdoms of life. Plant viruses have obvious importance for food crops and ornamental plants, and a range of viruses are responsible for an estimated $60 billion in crop losses worldwide each year.

To capture the astonishing richness of the planet's viral universe, researchers have gone beyond early methods of pinpointing individual virus particles and analyzing them. Techniques of metaviromics are used to probe environments for the full panoply of viruses they contain. The method, which relies on piecing together multiple DNA or RNA genomes from environmental samples, has been recently used to identify vast numbers of previously undocumented viruses. In the case of plant viruses, these viral fragments are often extracted from the insect vectors that ferry the viruses from plant to plant.

New methods uncover a welter of new viruses

Metaviromic sequencing is a particularly powerful technique for investigating viral communities. Unlike cellular life, which has a single, common origin, viruses are polyphyletic, meaning that they are the result of multiple origins. No single gene has been identified that is shared by all viruses. While common protein motifs have been observed in viral capsids, these are likely the result of convergent evolution or horizontal gene transfer, rather than inherited elements.

The strategy of metaviromics is particularly useful for teasing out mutualistic relationships between plants, vectors and viruses and their changing relationships over time. As so much research since the inception of virology has been focused on viruses as disease-causing agents in humans and plants, the nature and degree of mutualistic interactions between viruses, vectors and hosts is most likely underrepresented.

The authors speculate that viruses may play an important role in maintaining biodiversity and helping plants adapt to their environment by limiting the growth of genetically homogeneous plants, including crops. New studies of viral ecology seek to understand the extent and importance of both pathogenic and mutualistic interactions. An all-important link in the chain of infection is the behavior of particular insect vectors and their modes of viral transmission, though numerous other factors come into play, including nutrients, water resources, heat and cold stress, and adverse soil conditions.

Viral intermediaries

Vectors play an outsized role in the world of plant viruses. Unlike animal viruses, plant viruses are not usually transmitted through direct contact between infected and uninfected individuals. Instead, plant viruses disseminate through vectors, (especially insects) as well as through pollen and seeds.

It is believed that the mode of viral transmission plays a role in the virus' effect on its host. If the virus is transmitted via seeds or pollen, the virus should limit its harmful effect on the reproductive success of the host plant, perhaps even conveying an adaptive advantage over uninfected plants.

The viral passage from parent to daughter plant is known as vertical transmission. By contrast, horizontal viral transmission occurs when insect vectors transit the virus from plant to plant. Such vector-borne assaults can be more merciless to the infected plant and only need ensure their continued spread to a suitable number of healthy plants for the virus to be successful.

Many kinds of vectors can transmit plant viruses, including arachnids, fungi, nematodes, and some protists, though more than 70 percent of known plant viruses are transmitted by insects, most from the biological order Hemiptera, which includes cicadas, aphids, planthoppers, leafhoppers and shield bugs.

Insects of this kind can make use of mouthparts constructed for piercing and extracting sap or plant cell material. Insect transmission of plant viruses can occur through excretion of virus particles in saliva following feeding on an infected plant. Alternately, the plant virus can become permanently incorporated into the insect's salivary glands, allowing the vector to transmit the virus to new plants throughout the insect's lifetime.

Intriguingly, a number of insect-transmitted plant viruses may have evolved mechanisms to influence vector behavior, making infected plants more attractive to sap-feeding insects or ensuring that infected plants produce chemicals that promote insect behaviors that help facilitate transmission.

In addition to their complex and varied chains of infection, some plant viruses have another unique property. Such viruses transmit their genomes in multiple packets, each containing only part of the virus' complete genetic code, encapsulated in a separate virus particle. This peculiar strategy, which requires the co-transmission of several viral particles to a new host in order to ensure the integrity of the viral genome, is a feature believed to be unique to plant viruses. The nature and evolution of these so-called multipartite viruses remains a biological puzzle.

Plant viruses display considerable ingenuity in their strategies, which are highly dependent on their given environment. Some are generalists, invading multiple species, while other viruses are specialists that favour a narrow range of plant hosts. This selectivity may develop with time, through a process known as adaptive radiation. This typically occurs when a virus faces a heterogeneous habitat and becomes adaptively specialized to exploit particular ecological resources while becoming maladapted to exploit others. Such specialization acts to limit competition between different viral lineages or species. Alternatively, generalist viruses infect multiple plant hosts but must compete for these resources with other viruses. This situation tends to result in a viral population of low diversity dominated by the most acutely adapted viral genotypes.

The arrival of viruses

While researchers agree that viruses lack a single common ancestor, a detailed picture of how (and when) they emerged in the web of life remains deeply contested. Three common hypotheses compete for dominance as an explanatory framework, though they are not mutually exclusive. Perhaps viruses evolved from free-living cells, as the devolution or regressive hypothesis states. They could also have originated from RNA and DNA molecules that somehow escaped from living cells. Alternatively, viruses may have once existed as self-replicating entities that evolved alongside cells, eventually losing their independent status.

Ongoing metaviromic research of viral diversity is helping to uncover foundational relationships among viruses and pinpoint common origins among many plant, fungal and arthropod viruses. Of particular concern for the future are the ways in which human-caused disruptions to ecosystems across the planet, which are occurring at rates unprecedented in earth's history, are reforming virus, vector and host relationships.

The effects of these disruptions may be to foster emergent viruses with heightened abilities to cause disease in their hosts. As ecological communities become more tightly interwoven through changes in human land use, existing interaction networks that have acted over evolutionary time to stabilize host relations with native vectors and viruses can suddenly shift. Any lethal entity entering this kind of disrupted ecosystem is much likelier to rapidly spread through the population and aggressively sweep through different organisms. The future health and sustainability of both human and plant populations will benefit from an improved understanding of the many subtle interrelationships governing the most ubiquitous viruses--those colonizing plants.

BUFFALO, N.Y. -- University at Buffalo researchers have determined that a human gene present in 75 % of the population is a key reason why a class of drugs for Alzheimer's disease seemed promising in animal studies only to fail in human studies.

The researchers say the work suggests that in different Alzheimer's disease patients, different mechanisms are at work that determine whether or not a given therapy will be effective.

While a previous study by the researchers studied the function of the gene in tissue culture, this is the first time that drug effect based on a patients' genotype has been clinically shown.

The UB researchers caution that the study has its limitations and randomized double blind studies are needed to confirm the results.

The research was presented today at the annual Alzheimer's Association International Conference (AAIC) in Los Angeles. It was conducted on data from a ten-year, longitudinal, multicenter cohort study by the Texas Alzheimer Research and Care Consortium (TARCC) on 345 Alzheimer's patients. The UB researchers are collaborators on the TARCC.

Proof of concept

"This research provides proof of concept that since different mechanisms are at work in Alzheimer's in different patients, we need to develop more personalized treatments that will prove more effective in individuals," said Kinga Szigeti, MD, PhD, lead investigator, director of UB's Alzheimer's Disease and Memory Disorders Center, part of UBMD Neurology, and associate professor of neurology in the Jacobs School of Medicine and Biomedical Sciences at UB.

The gene, CHRFAM7A, is a fusion between a gene that codes for an Alpha 7 receptor for acetylcholine, a neurotransmitter involved in memory and learning and long associated with Alzheimer's, and a kinase, a type of enzyme.

Szigeti explained that the gene is present in two flavors, a functional gene and one that is not made into protein, data the UB team also is presenting this week at AAIC.

"This splits the population 1-to-3 between non-carriers and carriers," said Szigeti. CHRFAM7A has been implicated in many neuropsychiatric disorders, such as schizophrenia and bipolar disease.

Szigeti explained that three of the four drugs now available for Alzheimer's work by stimulating all receptors that respond to acetylcholine. More specific drugs for Alpha 7 have been in development for over 10 years but failed when moved to the clinical phase.

The human fusion gene modulates the Alpha 7 receptor, one of the receptors binding amyloid beta, the protein that is the hallmark of Alzheimer's that disrupts neuronal communication.

"Since this human fusion gene was not present in the animal models and screening systems used to identify drugs, 75 % of Alzheimer's patients who do carry this gene are less likely to benefit and therefore are at a disadvantage," she said. "This may account for the translational gap."

Gene carriers

"With this study, we compared the effect of cholinesterase inhibitors in patients who did or didn't carry this gene," said Szigeti. "People who don't have the gene respond better to the drugs available now."

She added that neurons vulnerable to Alzheimer's express Alpha 7 and that may be the reason why they die first.

"Our work confirms that Alpha 7 is a very important target for treating Alzheimer's but the right model--a human model--has to be used when testing new drugs," said Szigeti.

ANN ARBOR--Roughly 11% of high school seniors reported prescription drug misuse during the past year, and of those, 44% used multiple supply sources, according to a pair of University of Michigan studies.

More than 70% of adolescents who obtained prescription drugs from multiple sources had a substance use disorder--involving prescription medications, other drugs and alcohol--within the previous year.

The national average for a substance use disorder for all adolescents is 5%, said senior author Sean Esteban McCabe, a professor at the U-M School of Nursing.

Both studies, published in the July issue of the Journal of the American Academy of Child and Adolescent Psychiatry, found that adolescents using multiple sources for prescription medications were at high risk for other substance use and substance use disorders, among other disturbing patterns.

One study identified sources of misuse for three classes of prescription drugs--opioids, stimulants and tranquilizers--and the differences in motives and behavior among 18,549 high school seniors. The other study identified sources of controlled medications and related behaviors in 103,920 adolescents ages 12 to 17.

A "very concerning" finding is that 30% of prescription drug misusers took their own leftover medication, with girls more likely to take leftovers than boys, said McCabe, who is also co-director of the U-M Center for the Study of Drugs, Alcohol, Smoking and Health. Boys were more likely to obtain prescription drugs from friends or purchase them.

The most common sources for prescription drugs for 12-to-17-year-olds were getting them free from friends and relatives, physician prescriptions for opioids, and buying stimulants and tranquilizers illegally.

"These adolescents are most in need of intervention to address their substance use and any other medical and mental health issues," said Ty Schepis, associate professor at Texas State University and lead author of one of the studies.

This is the first known research to look at adolescent misuse of leftover medications across these three prescription drug classes, McCabe said.

"The implications from these two studies could not be clearer," McCabe said. "Parents, public health experts and clinicians must rally to address this problem. There is a critical need for clinical workforce training to support clinic and school-based education, screening, prevention and early intervention."

The concept of a carbon budget has become a popular tool in guiding climate policy since the Intergovernmental Panel on Climate Change's (IPCC) Fifth Assessment Report was released in 2014. IIASA researchers were involved in the development of a framework that can help scientists determine which factors affect the size of the remaining carbon budget and how they interact.

Research over the course of the past decade has shown that global warming is more or less proportional to the total amount of CO2 released into the atmosphere. This makes it possible to estimate the total amount of CO2 we can still emit while having a chance to limit global warming to a certain level - a concept known as the remaining carbon budget. The simplicity of the notion has made it an attractive tool for policymakers, even though it is strongly dependent on the assumption of a linear relationship between global temperature rise and cumulative CO2 emissions due to human activity. Given that we are aiming to keep warming well below 2°C and preferably even below 1.5°C, this is an extremely important number to inform decision makers about how rapidly we have to bring our emissions down to zero.

As low-carbon policies and technologies continue to advance, policymakers, companies, and investors are increasingly relying on carbon budgets as a core component for analyzing the potential implications of a carbon constrained future. Over the past couple of years, several estimates were published that all differed to a greater or lesser extent due to reasons that were previously not well understood. We know that global warming is not driven by CO2 emissions alone - other greenhouse gases such as methane, fluorinated gases, nitrous oxide, and aerosols also affect global temperatures, and estimating remaining carbon budgets therefore also implies making assumptions about these non-CO2 contributions. This added uncertainty and decreased the use of the linear relationship between warming and cumulative emissions of CO2 for target setting.

In their study published in Nature, researchers from IIASA and colleagues from among others, the Grantham Institute at Imperial College London, the University of Leeds, MeteoFrance, and the Potsdam Institute for Climate Impact Research, provide a way to understand and track changes in the remaining carbon budget. The framework they propose in their paper can also provide a way to better understand how this number might change in the future and contribute to a more constructive and informed discussion of the topic, while also facilitating better communication across disciplines and communities that research, quantify, and apply estimates of remaining carbon budgets. The study defines the size of the remaining carbon budget by five main factors. These are the amount of warming expected per ton of CO2 emission; the amount of warming observed until today; the amount of future warming expected from gases other than CO2; whether warming stops instantly once CO2 emissions get to zero; and an additional correction for whether there are any additional reinforcing cycles in the Earth system that have not been considered sufficiently.

"Our paper provides a new tool to clearly communicate up to date insights about carbon budgets. With the framework, changes can be pinpointed to single contributions that are much easier to understand. This should increase confidence in carbon budget estimates among policymakers, or at least their advisors, because changes in carbon budget estimates cease to appear to be random but rather are the result of clear progress of science in various areas," explains Joeri Rogelj, a senior researcher with the IIASA Energy Program and lead author of the study.

According to the researchers, their framework can play a role in contextualizing new estimates in the future, even if they use alternative methods. It can also be used in combination with expert judgment to anticipate potential surprise changes in remaining carbon budgets and allow for a more independent assessment by drawing on multiple lines of evidence. A simplified version of this framework was already applied in the recent IPCC Special Report on Global Warming of 1.5°C.

"The remaining carbon budget is a key quantity for defining the challenge of limiting climate change to safe levels. With this paper, we can understand and track this quantity much better. If you carefully look at carbon budgets, they become easy to understand. The fog is lifted, so to speak, and shows even more clearly that the remaining carbon budget to limit global warming to safe levels is tiny - action in the next decade is essential to stay within it," concludes Rogelj.