Culture

What The Study Did: Survey responses from a nationally representative group of 800,000 U.S. adults were used to examine changes in heroin use, heroin injection and heroin use disorder from 2002 to 2018.

To access the embargoed study: Visit our For The Media website at this link https://media.jamanetwork.com/

Authors: Beth Han, M.D., Ph.D., M.P.H., of the Substance Abuse and Mental Health Services Administration in Rockville, Maryland, is the corresponding author.

(doi:10.1001/jama.2019.20844)

Editor's Note: The article includes conflict of interest and funding/support disclosures. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.

Some people are annoyingly good at "reading between the lines". They seem to know, well before anyone else, who is the killer in a movie, or the meaning of an abstract poem. What these people are endowed with is a strong inference capability - using indirect evidence to figure out hidden information.

But inference is not a skill possessed by the lucky few. On the contrary - we all use inference regularly, we just don't realize it because it comes so naturally to us. It has been crucial for our survival as a species ever since the early days, when we used it to figure out when and where to search for food. For instance, we used indirect evidence, such as faint rustling sounds in the vegetation, or the presence of half-eaten leaves, to infer that a rabbit must be near.

Even though inference plays such an important role in our lives, neuroscientists have long struggled to understand how it is actually generated in the brain. One approach has been to design experiments that tap into this cognitive skill in rodents, who are much more like us than most people realize.

However, designing experimental tasks to probe inference in rodents has proven to be a challenge. While some tasks turned out to be too difficult, others gave ambiguous results, as they could also be solved with less sophisticated strategies.

Now, scientists at the Champalimaud Centre for the Unknown in Lisbon, Portugal, found a way out of the crux. In their study, published today (February 11th) in the scientific journal Neuron, the team presents their elegant experimental design, along with an identification of key brain regions involved, and a matching video-game version for humans.

A puzzle worthy of a mouse detective

What ingenious element makes the new experimental design succeed where others have failed? Zachary Mainen, the principal investigator that headed the study, believes the reason is that it is more compatible with the mice's nature. "Instead of imposing conditions where the mice would have to behave like 'little humans', we decided to create a task that will feel more natural to the mouse, relying on its innate foraging skills. The same skills it relies on when searching for food or water."

In the experiment, mice had to use inference to discover the location of a water reward. "The water reward could, at any given moment, be available at one of two water spouts. If the mice were successful in piecing together the evidence, they would optimize their behavior; switching between spouts to receive a reward with minimal delay", Mainen explains.

The location of the reward was controlled by two independent variables, both of which were unknown to the mice. "The mice had to infer what those variables were by trial and error, gradually deciphering the rules of the game", says Pietro Vertechi, an author of the study.

The first variable was the probability of receiving water at the active water spout. "Even when a spout was active, it didn't always give water. The mice had to realize that the lack of water on any given try didn't necessarily mean that the spout wasn't active", Vertechi explains.

The second variable added more complexity to the task: the probability that the spouts would switch between the active and the inactive state (which effectively means switching the location of the reward) was set at a certain value, which the mice also had to figure out.

This design enabled the researchers to control precisely how challenging the experiment would be. For instance, a relatively easy scenario would have high probabilities of both receiving a water reward and of a location switch. In that case, lack of a water reward would likely mean that the mouse was at the wrong spout.

On the other hand, it would be much more difficult for the mice to decide what to do if both probabilities were low. In that case, lack of water on a given try wasn't a very strong indication that switching had happened.

Sniffing out the rules of the game

Surprisingly, the mice were able to figure out quite quickly what was going on. "They optimized their behaviour within few sessions", says Vertechi, "adjusting the number of attempts at a spout according to the rules of the game. As a result, they tolerated many more failures in the hard, uninformative condition than in the easy one."

It is indeed very impressive that mice could master this complex task. But how did the researchers show that these results were compatible with inference and not another problem-solving strategy?

According to Eran Lottem, an author of the study, the standard strategy rodents are thought to apply would have resulted in a completely different outcome. "Researchers generally believe that mice are driven by the direct rate of reward. If that was the case, they would just stay at the spout that gave them more reward on average, and keep trying for much longer at that spout, even after it had become inactive. Instead, our mice switched as soon as they were certain that their spout was no longer active, no matter how rewarding it had been in the past. This strongly supports that what the mice were doing was inference."

Mouse versus human

To directly compare performance across species, the team developed a version of the task for humans. "This is also a kind of a 'foraging' task, but this time, instead of searching for water, the subjects were searching for prey", says Dario Sarra, another author of the study.

In the human version, subjects played a video game in which the hidden information was the location of a monster that was hiding behind a castle. The goal was to hit the monster by throwing rocks. Just like the mice, the subjects had to figure out two sets of variables: the probability of being able to hit the monster when in the right location, and the probability of a location switch.

Their results demonstrated that mice and humans solve the task in a remarkably similar manner. "Not only was the strategy practically exactly the same, we found that both species are sensitive to the same challenges", says Sarra. "Specifically, the inference process took longer, in both species, when the probabilities of reward and state-switch were low, creating overall higher uncertainty. However, regardless of difficulty, humans figured out what was going on much faster than the mice, reaching optimal performance already in the first session."

According to Mainen, their results imply that "video games make mice out of us. Some video games, like the one we developed, tap into fundamental behaviors, in this case foraging. We were surprised to find that both species behaved so similarly. But then again, it just goes to show how much these two species have in common."

Next steps

The team intends to use the human and the mouse versions of the task as a tool to study the neural mechanisms underlying this cognitive process. "In this study, we already started exploring some of these questions. Particularly, we observed that a brain area called the orbitofrontal cortex played a key role in the inference process. In trials where the orbitofrontal cortex was inactivated, mice reverted to a simpler, more naive strategy. This is an exciting finding, that will help us move forward with deeper investigation into how inference happens in the brain", says Mainen.

In addition, the team is curious to see whether the video game version of the task could be used to characterize specific psychological profiles. "For instance", Vertechi explains, "Do people that suffer from impulse control disorders, or depression, tend to adopt specific strategies? If we find that the answer to this question is yes, then we could take advantage of the analogous rodent task to assess neural mechanisms underlying these specific profiles", he concludes.

WASHINGTON, February 11, 2020 -- Duchenne muscular dystrophy is the most common type of muscular dystrophy, affecting more than 10,000 males at birth per year in the United States with severe physical disability, chronic wasting and muscle deterioration.

Testing through MRIs, gene testing or muscle biopsy requires specialized equipment, invasive procedures and high expense, but measuring changes in muscle function and identifying compensatory walking gait in young boys could lead to earlier detection.

This week in Chaos, from AIP Publishing, the authors present an index called a relative coupling coefficient, which can be used to quantify the factors involved in the human gait and more accurately screen for Duchenne muscular dystrophy. Using inexpensive inertial sensors, they measured the movements of different parts of the body in test subjects, viewing the body as a kinematic chain.

"In sports science, the theory of kinematic chain is the most classical one in explaining the transmission of human body power," author Jian An said. "In the process of movement, different links complete the corresponding actions, according to the specific structure at a given time, in order to maintain the relative dynamic stability of the body."

In the study, accelerometers were placed on participants in five locations: both forearms, both leg flanks and the core of the body. As participants walked, time series data was collected to create a core-limb coupling coefficient, which compares core and limb data, and a homolateral-limb coupling coefficient, which compares data from the forearm and leg flank. Combined, these provide a picture of the degree of coupling throughout the whole body.

The study focuses on human walking as a system of subsystems -- linked-up body parts that operate cooperatively in a nonlinear complex system. That means linear dynamics in statistical analysis do not describe it well, and nonlinear dynamics models are better suited to the task.

The authors use phase space reconstruction to capture the dynamics in the complex system of the human gait pattern. Their work is based upon Takens' embedding theory, which allows them to extract the embedding dimension in a one-dimensional time series dataset. The result is a data-infused methodology for screening for Duchenne muscular dystrophy.

The authors plan to continue their work to improve the ability of the relational coupling coefficient to increase its accuracy as a tool for diagnosis, as well as developing applications for elderly people, such as predicting fall risk.

Florida has experienced numerous harmful algal blooms in recent years, including blue-green algae and their toxins in 2016 and 2018. Despite their intensity and frequency, there is scant data on human exposure to these blooms and concentrations of the toxins they produce in tissues of exposed individuals. The most common routes of human exposure to these toxins include direct contact, ingestion and inhalation. Little is known about airborne exposure to these toxins in recreationally and occupationally exposed humans.

A study led by researchers at Florida Atlantic University's Harbor Branch Oceanographic Institute in collaboration with FAU's Christine E. Lynn College of Nursing and Colorado State University, was recently published in the journal Harmful Algae. The results provide evidence of aerosol exposure to microcystins among coastal residents.

Researchers detected microcystin, the main class of cyanotoxins produced by blue-green algae species, in the nasal passages of 95 percent of the participants. Some of these individuals reported no direct contact with impacted water. Therefore, these findings may be due to the aerosolization of cyanobacteria and transport in the air as has previously been hypothesized.

"Aerosolized cyanotoxins represent an important potential route of exposure and should be included in risk assessments for human populations," said Adam Schaefer, M.P.H., lead author and an epidemiologist at FAU's Harbor Branch. "Our study represents an essential first step in assessing and mitigating the potentially harmful effects of cyanobacteria blooms. We have a lot of unanswered questions to address regarding absorption of toxins, the minimum safe distance for persons from blooms, and potential health effects of exposure."

The recently proposed limit of microcystins to minimize human health risks associated with direct contact with water through recreation and swimming was set at eight parts per billion by the United States Environmental Protection Agency. However, there are currently no limits specific to airborne concentrations of microcystins or inhalation guidelines.

Researchers also found higher concentrations among occupationally exposed individuals. The significantly higher nasal concentration among individuals whose job regularly brought them into contact with impacted bodies of water is an important finding. To date, little has been done to assess occupational exposure to blue-green algal blooms.

There were no significant differences in the mean microcystin concentration by gender, race, or level of education achieved. Individuals who reported having direct contact with impacted water such as boating and fishing in the past 24 hours had a significantly higher mean nasal microcystin concentration than those with no direct contact during that timeframe.

"Ninety-five percent of the individuals screened had a nasal microcystin concentration above the detection limit of the assay," said Schaefer. "Only individuals screened at the end of the bloom period showed negative results. A relationship between nasal and water microcystin concentrations also was demonstrated."

Study participants were recruited at public locations near Stuart, which is located at the mouth of the St. Lucie estuary downstream from Lake Okeechobee, between July 30 and Sept. 30, 2018. After completing a questionnaire, sterile cotton swabs were used to collect a sample from the nasal mucosa, which were analyzed for microcystin concentration. Concurrently, researchers collected and analyzed a total of 47 surface water samples, collected bi-weekly during that same timeframe. Environmental concentrations of microcystin in water samples were analyzed by sampling location and sampling week to correspond with human sampling locations and dates.

"Recent funding from the Florida Department of Health will allow us to expand this research to evaluate the potential long-term health effects of exposure to blue-green and red tide algae at multiple sites in the state," said Schaefer.

Study co-authors are James Sullivan, Ph.D., executive director of FAU's Harbor Branch; Luke Yrastorza, Nicole Stockley, Robert Grady, and Malcolm McFarland, Ph.D., all with FAU's Harbor Branch; Kathi Harvey, FAU's Christine E. Lynn College of Nursing; and John S. Reif, D.V.M, Department of Environmental and Radiological Health Sciences, Colorado State University.

"Analysis of other tissues also is needed to establish inhalation as an important route of exposure and systemic absorption," said Sullivan. "This study is a critical step in our ongoing efforts of the Center for Coastal and Human Health to understand and protect against the potential human health effects of harmful algal blooms."

Many popular guitar amplifiers and distortion effects are based on analogue circuitry. To achieve the desired distortion of the guitar signal, these circuits use nonlinear components, such as vacuum tubes, diodes, or transistors. As music production becomes increasingly digitised, the demand for faithful digital emulations of analogue audio effects is increasing.

Professor Vesa Välimäki explains that this is an exciting development in deep learning, 'Deep neural networks for guitar distortion modelling has been tested before, but this is the first time, where blind-test listeners couldn't tell the difference between a recording and a fake distorted guitar sound! This is akin to when the computer first learned to play chess'.

The main objective of the field of Virtual Analog (VA) modelling is to create digital emulations of these analogue systems which will allow bulky, expensive and fragile analogue equipment to be replaced by software plugins that can be used on a modern desktop or laptop computer.

A specific amplifier's circuitry can be accurately simulated using circuit modelling techniques, but the result is often a model that is too computationally demanding for real-time processing. Additionally, a new model has to be created for each amplifier being modelled, and the process is labour intensive.

An alternative approach for VA modelling is "black-box" modelling. Black-box modelling is based on measuring the circuit's response to some input signals and creating a model which replicates the observed input-output mapping. The study from which these results came, was based on the WaveNet convolutional neural network.

The digital amplifier model is created using a deep neural network. Audio is recorded from a 'target 'guitar amplifier, and this audio is used to train the deep neural network to simulate that guitar amplifier.

Alec Wright, a doctoral student, focusing on audio processing using deep learning says,' The tests were conducted to validate the performance of models emulating either the Blackstar HT5 Metal or Mesa Boogie Express 5:50+ tube amplifiers. The models were created with a focus on real-time performance, and all of them can be run in real-time on a desktop computer'.

All of this means that in the near future, all a guitarist will need to do is plug into their laptop that is running the deep neural plugin, and a thoroughly convincing vintage guitar amp sound will come from the speakers.?

It remains to be seen if guitar amplifier purists will be willing to part with their beloved rigs, but this innovation paves the way for any audio enthusiast to digitally get the desired guitar sound, whether it be a Marshall, Orange, Fender, or anything else, on the road or in the studio.

https://www.aalto.fi/en/aalto-acoustics-lab

New research has found that bush-crickets' ear canals have evolved to work in the same way as mammals' ears to amplify sound and modulate sound pressure - and the findings could help scientists make better acoustic sensors for human use.

Bush-crickets are insects that depend on acoustic communication for survival, with the males singing to attract distant females. They have very small 'ears' in their forelegs, which work in a similar way to humans with an outer, middle and inner ear, and many species have transparent 'skins', enabling scientists to measuring ear processes.

An international team of sensory biologists and mathematicians found that the insects' horn-shaped outer ear, called the acoustic trachea tube, captures sound in the same way as mammals' ear canals by amplifying and transforming the pressure waves, which are then passed along to the surface of the eardrum to provide the animal with directional hearing.

Until now, the mechanism responsible for such changes in sound pressure levels which affects directional hearing has been unknown. The findings could revolutionise how auditory devices identify the location or origin of a detected sound, aiding the challenging design of wireless acoustic sensor networks used for monitoring and surveillance purposes.

The team carried out the study on a species called Copiphora gorgonensis, which are found in the Colombian rainforest. They used 3D x-ray imaging to capture the structure of the bush-cricket's ears, coupled with mathematical analysis to determine how the sound worked inside the acoustic tube.

The research was part of a €1.9million European Research Council-funded project led by Professor Fernando Montealegre-Zapata, an entomologist specialising in sensory biology and biophysics at the University of Lincoln, UK. It was carried out in partnership with the University of Bristol, and University of Graz in Austria.

Dr Emine Celiker, a Research Fellow in numerical modelling in the School of Life Sciences at the University of Lincoln, conducted the study. She said: "The research is the first step in using combined experimental and mathematical techniques to determine the mechanism crickets use to hear their species' songs.

"Our findings provide a strong indication that the bush-cricket ear processes sound in the same way a mammal's does, making its study vital for the development of new auditory sensors. We were able to take recordings of the auditory process using laser doppler vibrometry which measures the vibrations of soundwaves on the surface of the ear canal.

"By applying mathematical modelling of the ears combined with real-life experiments, we also found that the ear canal filters out sound frequencies relevant to the species' survival, selectively amplifying only frequencies that are behaviourally relevant for the animals - like their mating song or the high-frequency calls of predatory bats.

"Traditionally it is well known that horns increase the volume of sound, and for bush-cricket hearing it has been suspected that this is also the case due to the geometry of its acoustic tube. We verified this after a thorough investigation of the processes involved in the sound amplification. The findings have huge potential to be applied in enhancing acoustic sensors such listening devices."

The findings have been published in Biophysical Journal.

People age in different ways. Biological age is a metric that scientists use to predict health risks, the relevance of which can be enhanced by combining different markers. Particularly important markers are frailty and the epigenetic clock, write researchers from Karolinska Institutet in a study published in eLife.

Biological age can differ from chronological age, and the idea of measuring biological age is that it can indicate health risks or the risk of early death - and thus hopefully provide new opportunities for preventative healthcare.

But which markers are most relevant to the measurement of biological age? One new piece of the puzzle can be found in a study led by Sara Hägg, researcher at Karolinska Institutet, that combined different markers.

"There are different ways of measuring biological age," she says. "We need to know which markers are the most important. Ultimately it might conceivably lead to new ways to prevent age-related diseases."

The biological age metric has been examined in several studies recently. One thing that sets this new study apart is that it studies a combination of multiple markers.

The results of the study show that some markers are particularly important for predicting the risk of early death. The degree of frailty, based on the participants' self-reports of various symptoms, is one; another is the epigenetic clock (DNA methylation age estimator), which is linked to how different genes are expressed.

Other markers studied include telomere length, blood biomarkers and cognitive and physical abilities. These markers were also associated with an increased risk of early death.

The study was a population study that followed 845 middle-aged and elderly participants over a period of 20 years.

"There is a lot of interest in this research and biological age is an effective tool for predicting health risks," says Hägg. "However, it's important to stress that our results are population-based and need to be validated at an individual level."

Therapeutic cancer vaccines were first developed 100 years ago and have remained broadly ineffective to date. Before tangible results can be achieved, two major obstacles must be overcome. Firstly, since tumor mutations are unique to each patient, cancer cell antigens must be targeted extremely precisely, which is very hard to achieve. Secondly, a safe system is needed to deliver the vaccine to the right location and achieve a strong and specific immune response.

Li Tang's team at EPFL's School of Engineering is coming up with a solution to the delivery problem. The researchers have used a polymerization technique called polycondensation to develop a prototype vaccine that can travel automatically to the desired location and activate immune cells there. The patented technique has been successfully tested in mice and is the topic of a paper appearing in ACS Central Science. Li Tang has also co-founded a startup called PepGene, with partners that are working on an algorithm for quickly and accurately predicting mutated tumor antigens. Together, the two techniques should result in a new and better cancer vaccine in the next several years.

Helping the body to defend itself

Most vaccines - against measles and tetanus for example - are preventive. Healthy individuals are inoculated with weakened or inactivated parts of a virus, which prompt their immune systems to produce antibodies. This prepares the body to defend itself against future infection.

However, the aim of a therapeutic cancer vaccine is not to prevent the disease, but to help the body defend itself against a disease that is already present. "There are various sorts of immunotherapies other than vaccines, but some patients don't respond well to them. The vaccine could be combined with those immunotherapies to obtain the best possible immune response," explains Li Tang. Another advantage is that vaccines should reduce the risk of relapse.

But how does it all work?

Avoiding getting lost in the blood stream

Delivering a cancer vaccine to the immune system involves various stages. First, the patient is inoculated with the vaccine subcutaneously. The vaccine will thus travel to the lymph nodes, where there are lots of immune cells. Once there, the vaccine is expected to penetrate dendritic cells, which act as a kind of alert mechanism. If the vaccine stimulates them correctly, the dendritic cells present specific antigens to cancer-fighting T-cells, a process that activates and trains the T-cells to attack them.

The procedure appears simple, but is extremely hard to put into practice. Because they are very small, the components of a vaccine tend to disperse or be absorbed in the blood stream before reaching the lymph nodes.

To overcome that obstacle, Li Tang has developed a system that chemically binds the vaccine's parts together to form a larger entity. The new vaccine, named Polycondensate Neoepitope (PNE), consists of neoantigens (mutated antigens specific to the tumor to be attacked) and an adjuvant. When combined within a solvent, the components naturally bind together, forming an entity that is too large to be absorbed by blood vessels and that travels naturally to the lymph nodes.

Once inside a dendritic cell, the vaccine components separate again. This enables the dendritic cell to present the right antigens to the T-cells, causing a powerful immune response. "This new vaccine, combined with a highly advanced analysis of each patient's neoantigens, should allow cancer patients' immune systems to be activated in a personalized and safe way," says Li Tang.

The team is still perfecting the stage at which the tumor-specific antigens are detected. "This identification stage is just as vital," concludes Li Tang. "Since these neoantigens aren't present in healthy cells, accurate identification will allow us to target tumor cells very precisely, without any toxicity in healthy tissue."

Researchers at EPFL and MARVEL have developed a novel formulation that describes how heat spreads within crystalline materials. This can explain why and under which conditions heat propagation becomes fluid-like rather than diffusive. Their equations will make it easier to design next-generation electronic devices at the nanoscale, in which these phenomena can become prevalent.

Fourier's well-known heat equation describes how temperatures change over space and time when heat flows in a solid material. The formulation was developed in 1822 by Joseph Fourier, a French mathematician and physicist hired by Napoleon to increase a cannon's rate of fire, which was limited by overheating.

Fourier's equation works well to describe conduction in macroscopic objects (several millimeters in size or larger) and at high temperatures. However, it does not describe hydrodynamic heat propagation, which can appear in electronic devices containing materials such as graphite and graphene.

One of these heat-propagation phenomena is known as Poiseuille heat flow. This is where heat propagates within a material as a viscous-fluid flow. Another phenomenon, called "second sound," takes place when heat propagates in a crystal like a wave, similar to the way in which sound spreads through the air.

Since these phenomena are not described by Fourier's equation, until now researchers have analyzed them using explicit microscopic models, such as the Boltzmann transport equation. However, the complexity of these models means that they cannot be used to design complex electronic devices.

This problem has now been solved by Michele Simoncelli, a PhD student at EPFL, together with Andrea Cepellotti, a former EPFL PhD student now at Harvard, and Nicola Marzari, the chair of Theory and Simulation of Materials in the Institute of Materials at EPFL's School of Engineering and the director of NCCR MARVEL. They showed how heat originating from the atomic vibrations in a solid can be described rigorously by two novel "viscous heat equations", which extend Fourier's law to cover any heat propagation that is not diffusive.

"These viscous heat equations explain why and under which conditions heat propagation becomes fluid-like rather than diffusive. They show that heat conduction is governed not just by thermal conductivity, as described by Fourier's law, but also by a second parameter, thermal viscosity," says Simoncelli.

This breakthrough, published in Physical Review X, will help engineers design next-generation devices, particularly those that feature materials such as graphite or diamond in which hydrodynamic phenomena are prevalent. Overheating is the main limiting factor for the miniaturization and efficiency of electronic devices, and in order to maximize efficiency and predict whether a device will work - or simply melt - it is crucial to have the right model.

The results obtained by EPFL's team are timely. From the 1960s until recently, hydrodynamic heat phenomena had only been observed at cryogenic temperatures (around -260oC) and were therefore thought to be irrelevant for everyday applications. Already in 2015 Marzari and his colleagues predicted that this would be very different in two-dimensional and layered materials - a prediction that was confirmed with the publication in Science of pioneering experiments that found second-sound (or wavelike heat propagation) in graphite at temperatures around -170oC.

The formulation presented by the EPFL researchers yields results that line up closely with those experiments. Most important, they also predict that hydrodynamic heat propagation can also happen at room temperature, depending on the size and type of material.

Through their work, the EPFL researchers are providing new and original insight into heat transport, but also laying the groundwork for an understanding of shape and size effects - not only in next-generation electronic devices but also in "phononic" devices that control cooling and heating through engineered superstructures. Finally, the novel formulation can also be adapted to describe viscous phenomena involving electrons discovered in 2016 by Philip Moll, now a professor at EPFL's Institute of Materials.

When it comes to memory, immune cells are known as the "bad cops" of the brain. But new research shows they could also be turned into "good cops" to power memory and learning.

Inflammation can send the brain's immune cells into damaging hyperdrive, and this has been linked to neurodegenerative diseases that affect memory, like dementia.

In the new study, researchers at RMIT University found that these same immune cells - known as microglia - can also be activated to have the reverse effect.

When the microglia were altered in rats, their performance in simple memory tasks improved by up to 50%, rather than deteriorating.

While the effect was temporary, the discovery suggests these cells could be targeted in the development of new therapies designed to enhance memory formation, with the hope of preventing cognitive decline as people grow older.

Worldwide, around 50 million people have dementia, with nearly 10 million new cases each year. In Australia, dementia and ageing-related cognitive decline affect 9% of people aged over 65.

Chief Investigator and senior author, Associate Professor Sarah Spencer, said the unexpected results of the study expanded our understanding of memory formation and the role of neuroinflammation in memory loss.

"Cognitive decline is a big problem for our ageing population, and we currently have very few treatments to treat or prevent it," Spencer said.

"Even in healthy adults, optimising how well we learn and remember can give us a substantial performance edge at work and socially.

"Our study has for the first time shown a link between changes in the immune cells of healthy brains and improved cognitive function.

"While it's early days and a lot more research is needed, we hope our findings may lead to new therapies that can stimulate these immune cells to boost memory and keep our brains powering as we age."

Activating memory with activated microglia

In the study, published in Journal of Neuroinflammation, the researchers worked with a unique type of rat to test the effect of microglia on cognitive function.

The study looked how the rats performed memory tasks when the immune cells were present and compared this with their performance when almost all the microglia were knocked out.

They found that removing almost all the microglia made no difference in memory tasks.

But when the microglia regenerated, this led to astounding results: researchers ran the same memory tests on the rats and they performed 25-50% better than normal rats.

Importantly, the regenerated microglia were a different shape - similar to the "activated" shape that these cells have when dealing with inflammation.

"We are still exploring what makes these cells different when they repopulate the brain, but their shape tells us they may be more active than usual, potentially making the neurons more effective to encourage better memory," Spencer, an NHMRC Career Development Fellow at RMIT, said.

"The effect doesn't last. As the microglia go back to their usual shape, memory performance also goes back to normal.

"The next stage in the research is closely investigating these regenerated microglia to better understand the mechanisms at work, with the aim of finding ways to turn the temporary memory boost into a long-lasting effect."

Microglia-suppressing therapies are currently being tested in clinical trials in the US, as potential treatments for Multiple Sclerosis.

"With our new understanding of the role of microglia in memory, it may be possible in future to test the therapies originally designed for MS and assess their potential in improving cognitive function as well," Spencer said.

Spencer is a leading researcher in the Neurodevelopment in Health and Disease program at RMIT, a multi-disciplinary research group in the School of Health and Biomedical Sciences established to identify the determinants of healthy brain development, and early origins of neurological disease.

The round goby, one of the most common invasive freshwater fish in the world, boasts a particularly robust immune system, which could be one of the reasons for its excellent adaptability. This is the result of genome research by an international team of biologists, coordinated at the University of Basel and published in the journal BMC Biology.

With its stocky, spotted body, big eyes and large mouth, the round goby (Neogobius melanostomus) may not be the most attractive of aquatic creatures, but it is one of the most successful invasive species of fish. Within a few years, it has spread rapidly around the world. Usually introduced via the ballast water from ships, the fish has now become the dominant species in terms of numbers in various fresh and salt waters. Its marked ability to adapt to new environments is apparently related to its immune system, as the researchers report based on their genome analysis.

Up to 30 times more inflammation genes

For this analysis, the researchers read and assembled particularly long genome fragments from a round goby originating in Basel. Because of their length, these fragments produced an exceptionally complete genome, which was used to analyze gene families that were thought to relate to the fish's ability to deal with new environments. Here, the researchers described expansions in specific enzymes known as cytochrome P450.

Furthermore, the zoologists found that all the genes deployed in inflammatory immune responses are present in the fish - and, in some cases, up to 30 times more than in comparable species. This may help the round goby to deal with pathogens, thus favoring its successful colonization of waters around the world. But there is still one aspect that has the specialists puzzled: although round gobies are also found in highly polluted water - in ports, for example - they do not differ from other species in terms of detoxification.

Colder water than in their natural habitat

Furthermore, the researchers came across the genetic basis that allows the round goby not only to produce but also to accumulate osmolytes - substances that affect the osmotic state. These help the fish to deal not only with fluctuations in salinity but also with desiccation and cold. This could also explain why round gobies are also found in the Baltic Sea - that is, in water temperatures far below those of their original habitat.

Rabies is still responsible for approximately 60,000 human deaths per year mostly in Asia and Africa and affects especially underserved people. Yet, since the first vaccine developed by Louis Pasteur more than 130 years ago, prophylactic measures have significantly improved. They are now composed of the vaccine allied to purified human or equine rabies immunoglobulins. However, these immunoglobulins are expensive and not easy to reach in developing settings. Researchers from the Structural Virology Unit at the Institut Pasteur, in collaboration with the Virus and Immunity Unit and the Lyssavirus Epidemiology and Neuropathology Unit, have visualized one of the most potent and most broadly neutralizing human monoclonal antibody in interaction with the rabies glycoprotein. This finding makes it possible to propose new avenues, both prophylactic and therapeutic, in the fight against rabies.

Rabies is a lethal encephalitis due to a lyssavirus mainly transmitted to humans by the bite or scratches of terrestrial carnivores (principally domestic dogs). The onset of clinical symptoms and death can be 100% prevented by adequate post-exposure prophylaxis (PEP) including vaccines and passive immunization using rabies immunoglobulins (read our disease sheet). Today, 15 to 29 million of patients exposed to rabies received the PEP each year whose terms have been updated by WHO in 2018 as a result of Institut Pasteur expertise.

"If prevention measures therefore exist today to fight rabies, supply and demand are incoherent in developing countries. The proposed treatments are not produced or not available on site" explains Félix Rey, head of the Structural Virology Unit at the Institut Pasteur.

The RVC20 monoclonal antibody: a key-tool to understand the rabies virus

The rabies virus has only one glycoprotein (called G) exposed at its surface. This protein is responsible for the entry of the virus into the human cell and is therefore the only target of neutralising antibodies. In spite of its medical relevance, no structural data are available for the rabies virus surface glycoprotein.

"Here we report the structure of one of the most potent and most broadly neutralizing human monoclonal antibodies (mAb), named RVC20 in complex with the domain of G that it recognizes and binds" explains Hervé Bourhy, head of the Lyssavirus Epidemiology and Neuropathology Unit at the Institut Pasteur.

Researchers have described the crystal structure of the RCV20 antibody in complex with its target domain, one of the major antigenic sites of the rabies virus glycoprotein. The structure reveals that RVC20 involves highly conserved features of the viral glycoprotein, rationalizing its broad reactivity among the virus strains.

"We further show that RVC20 monoclonal antibody blocks the membrane fusion between the virus and the cell" says Hervé Bourhy. The antibody therefore blocks the entry of the virus into the cell and further spreading of the virus within the body of the infected host.

New perspectives for prevention and treatment

"Our study also highlights a major site of vulnerability at the virion surface, providing a mechanistic understanding of highly efficient rabies virus neutralization by the RVC20 antibody" summarizes Félix Rey. The new knowledge provided by this study could be employed not only for mAb-based prophylaxis, but also for future therapeutic applications in cases where the virus has already entered the nervous system and for which there is still no cure. "The idea behind these studies is being able to provide a substitute to the actual post exposure prophylaxis to protect against rabies" concludes Félix Rey.

The results of this study were made possible thanks to the collaboration of two platforms at the Center for Technological Resources and Research at the Institut Pasteur: the Crystallography Platform and the Molecular Biophysics Platform.

Gesture and prosody (stress, rhythm and intonation) play an important role in the development of children's communication skills. Studies have traditionally focused rather on the role played by these elements in the early acquisition of lexical and morphosyntactic elements and less at older ages, when children use prosody and gesture to express pragmatic meanings such as politeness.

"Despite evidence that children are sensitive to facial gestures and prosody for detecting emotions, until now there was conflicting evidence as to whether preschool children use these cues to deduce speakers' politeness", comments Pilar Prieto, an ICREA research professor at the Department of Translation and Language Sciences (DTCL) at UPF and principal investigator of a research area that has produced a study published in the advanced online edition of Journal of Politeness Research Language, Behaviour, Culture. A new study of which Iris Hübscher (University of Zurich, Switzerland and UPF) is first author and principal investigator, together withLaura Wagner, co-author, and researcher at Ohio University (USA).

In this study, the authors set out to investigate whether preschool children inferred a speaker's affective stance and degree of politeness taking into account the role of prosodic cues and facial expressions. This is the first study to show that 3-year-olds are sensitive to the meaning of politeness that is conveyed through intonation and facial cues.

For the study, they designed an experiment in which children listened to a request addressed to them of the type Can you hand me [this toy]? (either followed or not by please) delivered politely and impolitely. Thirty-six English-speaking US children aged three years participated in this experiment to find out if children deduced a speaker's politeness through intonation and/or facial gestures and in different formats, both audio mode and visually and in both modes simultaneously.

The results of the study show that children of aged three can be recognize politeness through the such prosodic cues as intonation, visual cues such as facial expressions, and the two together, and most importantly, unlike previous studies, the study shows that both intonation and facial expression are equally strong signals to make children understand the polite stance of a speaker.

This has implications for parents, carers and preschool teachers because it suggests gaining awareness of children's social and pragmatic behaviour, which often only focuses on verbal content", highlights Hübscher, the principal investigator of the study. Furthermore, Pilar Prieto also says that the study highlights the importance of sensitizing children to the great possible variety of expressions of politeness and not only to verbal contents such as the use of 'please'.

The authors point out that in the future it would be interesting to compare English-speaking American children with children who speak other languages, to see if these results are comparable or if there are intercultural differences in children's development in the understanding of politeness, as well as studying the development of politeness in broader age brackets.

People's values of personal choice, su?h as their attitudes towards abortion, divorce, and premarital sex, are usually determined their level of education, age, religiosity, and social status. At least this is the case in many countries such as the US and those in Europe. In a recent study, sociologists from HSE University and Max Planck Institute found that in post-Soviet countries, personal values are most determined by people's level of patriotism. http://jourssa.ru/?q=en/Lopatina%20et%20al_2019_4_Article

In post-Soviet countries, the transition from a planned economy to a market economy was accompanied by political instability and economic stagnation. Despite the fact that each country of the former socialist camp has had its own path of development, they are united by a prevalence of patriarchal and nationalist ideologies. When a nation is defined by ethnicity ('blood and soil'), as opposed to the constructivist approach, in which ethnicity and nation are considered to be politically constructed, an emphasis is often placed on primordial rhetoric.

The state propaganda of many post-Soviet societies places great importance on family values and fertility, while practices of individual choice, such as abortion, divorce, and premarital sex, are portrayed in the media and official discourse as dangerous to the nation and state.

In transitional societies that have experienced economic collapse or disintegration, the desire of elites to reconstruct national identity can lead to a revival of traditional values ?.

To test this postulation, sociologists analyzed data of the sixth wave of the World Values ??Survey, collected in 2014 from surveys of residents of ten former Soviet republics: Azerbaijan, Armenia, Belarus, Georgia, Estonia, Kazakhstan, Kyrgyzstan, Russia, Ukraine and Uzbekistan.

Scientists looked at the relationship between values of personal choice and national pride. http://jourssa.ru/sites/all/files/volumes/2019_4/Lopatina%20et%20al_2019_4.pdf

Approval of individual choice was measured on a scale of 1 to 10, where 1 indicated that a given decision 'can never be justified' and 10 indicated that a given decision 'was always justified'. The extent of a subject's nationalism was determined by two questions. The first question was, 'How proud are you that you are Russian (Belarusian, Uzbek, etc.)?' The second question regarded the main goals of the state. For this question, respondents had to choose from four options: 'military strength'; 'high level of economic growth'; 'improvement of the urban environment and rural regions'; and 'ensuring that the voice of ordinary people is taken into account when making decisions'. If a respondent answered that 'military strength' should be a state's main goal, then his or response was considered to be militaristically oriented. In addition, researchers took into account respondents' level of education, age, gender, religiosity, and marital status.

Post-Soviet Syndrome

Despite the prevalence of divorce, abortion and premarital sex in post-Soviet countries--Russia ranks first in the world in divorces (with 51% of marriages ending in divorce), while Kazakhstan, Belarus and Estonia rank among the world's top five countries for highest abortion rates--residents of these countries expressed conservative views on all three practices. Researchers, however, consider these expressions to be more a matter of lip service than actual practice. In their opinion, doublethink is characteristic of inhabitants of the former Soviet Union, where views that differed from those generally accepted were persecuted, and to this day remain in some places prosecuted by law and condemned by society. 'For example, homosexuality, which also falls under to purview of "values ??of individual choice" here, is so taboo in the post-Soviet context that it is almost impossible to study attitudes toward it,' notes Veronika Kostenko https://www.hse.ru/en/org/persons/26409382, one of the study authors. 'People are used to living in a system of double standards where people say one thing in public and another at home.'

The researchers found that the most significant predictor of conservative attitudes in all respondents was national pride. To the contrary, the other factors of gender, age, religiosity and education, if they did have any influence, did not do so in concert or consistently in every country.

For example, only in Armenia, Azerbaijan, Belarus, and to a lesser extent, Georgia, was there a relationship between having higher education and holding slightly less negative views towards abortion, divorce, and premarital sex. In other countries, including Russia, the factor had no effect.

Gender had some significance only in Armenia. There, women were less critical of values ??of personal choice less than men.

The researchers observed a link between age and values of personal choice among respondents from Belarus, Russia, and Ukraine. In these countries, older generations are less tolerant of abortion, divorce, and premarital sex. However, in Azerbaijan, Georgia, Kyrgyzstan, and Uzbekistan, researchers found no generational differences with regard to these questions.

In Estonia, Russia, and Ukraine, the more frequently an individual attends church, the more likely he or she is to reject values of individual choice. This is also the case, to a lesser extent, in Azerbaijan and Belarus.

As for marital status, divorced people turned out to be the most tolerant only in Azerbaijan, Uzbekistan, Belarus, Georgia, and Ukraine.

The influence of national pride is especially significant in Armenia, Belarus, Georgia, Kazakhstan, Uzbekistan, and, to a lesser extent, Estonia and Ukraine. In these countries, the higher the respondents' reported national pride, the stronger their rejection of the values of individual choice.

In Russia, Kyrgyzstan and Azerbaijan, militarism is more important than national pride. Respondents in these countries who did not approve of abortion, divorce, and premarital sex believed that military power should be their state's main goal.

Amsterdam, NL, February 11, 2020 - To better understand the relationship between physical activity and Parkinson's Disease (PD) investigators in Sweden analyzed medical records of nearly 200,000 long-distance skiers who took part in the Vasaloppet cross-country ski race. They established that a physically active lifestyle is associated with close to a 30% reduced risk for PD, which might be explained by a motor reserve among the physically active, however, this dissipates as individuals age. Their results are published in the Journal of Parkinson's Disease (JPD).

Studies have shown the enormous benefits of exercise in many disorders including neurodegenerative diseases, but the reasons are not always clear. "Exercise seems to protect against the motor symptoms of PD but not necessarily against the brain damage caused by PD," explained co-lead investigator Tomas T. Olsson, MD, Department of Neurology, Skåne University Hospital, and Department of Experimental Medical Science, Experimental Dementia Research Unit, Lund University, Lund, Sweden.

"To understand the mechanisms behind the protective effects of exercise it is very important to establish whether exercise gives people a greater reserve or direct protection," noted co-lead investigator Martina Svensson, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden.

To investigate the degree to which physical activity is associated with long-term lower risk of PD and whether this association can be explained by physically active people being able to sustain more PD neuropathology before the onset of clinical symptoms, investigators analyzed long-term data about the incidence of PD among long-distance skiers. They followed 197,685 participants (median age 36 years; 38% women) in the Vasaloppet, an annual cross-country ski race of up to 90 km, from 1989 to 2010 and compared them to 197,684 age-matched non-skiers. Incidence of PD was taken from the Swedish National Patient Registry

Investigators found that the skiers were almost 30% less likely to develop PD than non-skiers. However, this dissipates with time and increasing age and results in diagnoses of PD among skiers matching the general population.

"We speculate that this would be consistent with the hypothesis that individuals who are physically well-trained have a greater motor reserve, which for every given level of Parkinson's brain damage would result in less motor symptoms thus delaying the diagnosis of PD," noted senior investigator Tomas Deierborg, PhD, Department of Experimental Medical Science, Experimental Neuroinflammation Laboratory, Lund University, Lund, Sweden. "This is analogous to the well-established concept of cognitive reserve in dementia in which the well-educated can sustain more brain pathology without clinical dementia. It highlights the importance of staying physically active throughout life in order to have a reserve to better cope when the frailties and diseases of old age inevitably arrive."

"If a person is physically active, it may be possible to maintain mobility for longer, despite the pathological changes in the brain," added Dr. Olsson.

JPD's Co-Editor-in-Chief Bastiaan R. Bloem, MD, PhD, Director, Radboudumc Center of Expertise for Parkinson & Movement Disorders, Nijmegen, The Netherlands, commented, "There is an enormous interest in developing new therapies that can help to lower the risk of developing PD. This present study by Olsson and colleagues is particularly exciting in that regard, because it suggests that a readily available intervention - exercise - can actually achieve this. The study also provides an explanation why exercise does not offer a complete protection against PD; it supports the motor reserve of the brain, and as such, probably helps to postpone rather than fully prevent the onset of manifest Parkinson symptoms."

PD is a slowly progressive disorder that affects movement, muscle control and balance. It is the second most common age-related neurodegenerative disorder affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age.