Brain

Revisiting the Global Workspace orchestrating the hierarchical organisation of the human brain

The celebrations in the 250th anniversary of the birth of Ludwig van Beethoven would not be the same without Herbert von Karajan's brilliant performances conducting Beethoven's memorable symphonies. The execution of any musical symphony is a hugely difficult task, demanding very significant skills on the part of each individual musician - but perhaps the most difficult task lies with the conductor who has to orchestrate the musicians into making the music cohesively come alive and speak to our deepest emotions.

In many ways the human brain is like an orchestra, where different regions perform very different types of processing, such as in the individual musician in the orchestra who needs to be able to read the music, play their instrument and listen to the music produced. Still, the role of the conductor is different, namely to coordinate and orchestrate the output of each musician into a cohesive whole. Without a conductor, the music invariably fails - as shown beautifully in Fellini's magisterial film "Prova d'orchestra" (eng. "Musical rehearsal").

It has been proposed that the human brain is similar to an orchestra in that it is hierarchically organised but that there is unlikely to be just a single conductor. Instead, in 1988 psychologist Bernard Baars proposed the concept of a 'global workspace', where information is integrated in a small group of 'conductors' before being broadcast to the whole brain. This much celebrated theory proposes an elegant solution to how hierarchical organisation allows the brain to orchestrate function and behaviour by organising the flow of information and the underlying computations necessary for survival. As such, this is a theory of consciousness as pointed out by neuroscientists Stanislas Dehaene and Jean-Pierre Changeux, who proposed the 'global neuronal workspace' hypothesis where associative perceptual, motor, attention, memory, and value areas interconnect to form a higher-level unified space where information is broadly shared and broadcast back to lower-level processors. Colloquially, the brain's global workspace is thus akin to a small core assembly of people in charge of an organisation; in other words like a group of many Von Karajans leading a musical orchestra.

Yet, until now it has not been known where and how this orchestration takes place in the human brain. It is only with the new paper "Revisiting the Global Workspace orchestrating the hierarchical organisation of the human brain" published the leading open-access journal Nature Human Behavior on Monday 4th of January 2021 that researchers have discovered the existence of a functional 'rich club' of brain regions incarnating this 'global workpace'. This radical new discovery resulted from Profs Gustavo Deco and Morten L Kringelbach's international collaboration between Center for Brain and Cognition at University Pompeu Fabra, Barcelona (Spain) and Department of Psychiatry, University of Oxford (UK) and Center for Music in the Brain, University of Aarhus. Based on a large dataset of over 1000 human participants with functional magnetic resonance imaging (fMRI) recordings, the findings have shed new light on the nature of consciousness.

Prof Deco says: "To identify the global workspace, we determined the information flow between brain regions by means of a normalised directed transfer entropy framework applied to multimodal neuroimaging data a large group of healthy participants. This revealed for the first time a set of unique brain regions orchestrating information from perceptual, long-term memory, evaluative and attentional systems across many different tasks. Furthermore, we confirmed the causal significance and robustness of our results by systematically lesioning a generative whole-brain model".

Prof Kringelbach adds: "Our findings shed light on a major unsolved challenging problem in neuroscience. While the results presented here pertain to the global workspace of conscious task processing, future work could use our framework to investigate other states such as sleep and anaesthesia, allowing for a direct comparison with other theories of consciousness. Equally, our framework could be used to investigate unbalanced brain states in neuropsychiatric disorders and be used to perturb and rebalance the model to identify novel optimal, causal paths to health".

Credit: 
Universitat Pompeu Fabra - Barcelona

Controlling chemical catalysts with sculpted light

image: Depiction of the experimental setup where palladium nanorods lie atop gold nanobars. In this image, an electron beam is directed at the sample to watch the catalytic interactions between the hydrogen molecules (in green) and the palladium catalyst. The light driving the illumination is shown in red.

Image: 
Katherine Sytwu

Like a person breaking up a cat fight, the role of catalysts in a chemical reaction is to hurry up the process - and come out of it intact. And, just as not every house in a neighborhood has someone willing to intervene in such a battle, not every part of a catalyst participates in the reaction. But what if one could convince the unengaged parts of a catalyst to get involved? Chemical reactions could occur faster or more efficiently.

Stanford University material scientists led by Jennifer Dionne have done just that by using light and advanced fabrication and characterization techniques to endow catalysts with new abilities.

In a proof-of-concept experiment, rods of palladium that were approximately 1/200th the width of a human hair served as catalysts. The researchers placed these nanorods above gold nanobars that focused and "sculpted" the light around the catalyst. This sculpted light changed the regions on the nanorods where chemical reactions - which release hydrogen - took place. This work, published Jan. 14 in Science, could be an early step toward more efficient catalysts, new forms of catalytic transformations and potentially even catalysts capable of sustaining more than one reaction at once.

"This research is an important step in realizing catalysts that are optimized from the atomic-scale to the reactor-scale," said Dionne, associate professor of materials science and engineering who is senior author of the paper. "The aim is to understand how, with the appropriate shape and composition, we can maximize the reactive area of the catalyst and control which reactions are occurring."

A mini lab

Simply being able to observe this reaction required an exceptional microscope, capable of imaging an active chemical process on an extremely small scale. "It's difficult to observe how catalysts change under reaction conditions because the nanoparticles are extremely small," said Katherine Sytwu, a former graduate student in the Dionne lab and lead author of the paper. "The atomic-scale features of a catalyst generally dictate where a transformation happens, and so it's crucial to distinguish what's happening within the small nanoparticle."

For this particular reaction - and the later experiments on controlling the catalyst - the microscope also had to be compatible with the introduction of gas and light into the sample.

To accomplish all of this, the researchers used an environmental transmission electron microscope at the Stanford Nano-Shared Facilities with a special attachment, previously developed by the Dionne lab, to introduce light. As their name suggests, transmission electron microscopes use electrons to image samples, which allows for a higher level of magnification than a classic optical microscope, and the environmental feature of this microscope means that gas can be added into what is otherwise an airless environment.

"You basically have a mini lab where you can do experiments and visualize what's happening at a near-atomic level," said Sytwu.

Under certain temperature and pressure conditions, hydrogen-rich palladium will release its hydrogen atoms. In order to see how light would affect this standard catalytic transformation, the researchers customized a gold nanobar - designed using equipment at the Stanford Nano-Shared Facilities and the Stanford Nanofabrication Facility - to sit below the palladium and act as an antenna, collecting the incoming light and funneling it to the nearby catalyst.

"First we needed to understand how these materials transform naturally. Then, we started to think about how we could modify and actually control how these nanoparticles change," said Sytwu.

Without light, the most reactive points of the dehydrogenation are the two tips of the nanorod. The reaction then travels through the nanorod, popping out hydrogen along the way. With light, however, the researchers were able to manipulate this reaction so that it traveled from the middle outward or from one tip to the other. Based on the location of the gold nanobar and the illumination conditions, the researchers managed to produce a variety of alternative hotspots.

Bond breaking and breakthroughs

This work is one of the rare instances showing that it is possible to tweak how catalysts behave even after they are made. It opens up significant potential for increasing efficiency at the single-catalyst level. A single catalyst could play the role of many, using light to perform several of the same reactions across its surface or potentially increase the number of sites for reactions. Light control may also help scientists avoid unwanted, extraneous reactions that sometimes occur alongside desired ones. Dionne's most aspirational goal is to someday develop efficient catalysts capable of breaking down plastic at a molecular level and transforming it back to its source material for recycling.

Dionne emphasized that this work, and whatever comes next, would not be possible without the shared facilities and resources available at Stanford. (These researchers also used the Stanford Research Computing Center to do their data analysis.) Most labs cannot afford to have this advanced equipment on their own, so sharing it increases access and expert support.

"What we can learn about the world and how we can enable the next big breakthrough is so critically enabled by shared research platforms," said Dionne, who is also senior associate vice provost for research platforms/shared facilities. "These spaces not only offer critical tools, but a really amazing community of researchers."

Credit: 
Stanford University

45% of adults over 65 lack online medical accounts, which could affect COVID vaccination

As the vaccination of older adults against COVID-19 begins across the country, new poll data suggests that many of them don't yet have access to the "patient portal" online systems that could make it much easier for them to schedule a vaccination appointment.

The poll finds that 45% of adults aged 65 to 80, and 42% of all adults aged 50 to 80, said they had not set up an account with their health provider's portal system. That's according to the newly analyzed data from the National Poll on Healthy Aging, based at the University of Michigan's Institute for Healthcare Policy and Innovation.

The new number actually represents some progress: 49% of adults in the same age range hadn't set up patient portal access the last time the poll asked about this topic in March 2018.

Patient portals are secure online systems, linked to a health care provider's electronic medical record system, that patients can access using a computer or smartphone.

"Right now, one important thing that we can do for older adults is encourage and help them to sign up for patient portal access, or log in again if they haven't in a while, if their provider offers one, and especially if it will be used as part of the COVID-19 vaccination process," says Preeti Malani, M.D., director of the poll and an infectious disease physician at Michigan Medicine, the University of Michigan's academic medical center, which supports the poll along with AARP.

"If they don't have a computer, or they need help navigating the technology, they can appoint a trusted adult as their 'proxy' to access their account," she adds.

Disparities among those most affected by the pandemic

The new analysis shows wide gaps in patient portal use among different groups of older adults - with lower use by some of those who have the highest risk of a severe case of COVID-19 if they aren't vaccinated.

Just under 50% of Black older adults, and 53% of Hispanic older adults, lacked an account by June of 2020, compared with 39% of white older adults. Men were less likely than women to have signed up, though the gap has narrowed since 2018.

People age 65 to 80 were less likely to have a patient portal account compared with those aged 50 to 64, though use among both age groups has grown in the past two years.

The biggest gap was between adults with annual household incomes less than $60,000 a year, and those with higher incomes. About 54% of the lower-income older adults did not have a patient portal account, where only 35% of higher-income older adults lacked an account.

Meanwhile, 53% of those with less than a high school education lacked a patient portal account, compared with 31% of those who had graduated from college.

Vaccination notification and self-scheduling

As vaccine supply becomes more available, many public health authorities are encouraging older adults to turn to the health system that their primary care or specialist physicians are affiliated with for vaccination appointments.

"Vaccination is so critical to protect their health, and we don't want technology to stand in their way," Malani says. Both polls were carried out online in a national sample of more than 2,000 adults aged 50 to 80, and laptops and internet access were provided to poll respondents who did not already have them.

Malani notes that Michigan Medicine has begun notifying patients over 65 who have a MyUofMHealth.org portal account that they will receive notifications through the portal when it's their turn to arrange a vaccination appointment. When vaccine supply allows, they'll even be able to schedule that appointment directly through the portal, which is accessible on the web or via a smartphone app. Patients without portal accounts will receive mailed letters inviting them to schedule by phone.

Malani adds that health systems may not make vaccination appointments available until they have the vaccine on hand, and that delays in delivery have slowed the start of patient vaccination.

Michigan Medicine offers patients help with setting up an account via phone and email, and provides information for adult patients to grant proxy access to another adult to create a login and assist them.

Barriers and opportunities

In the 2018 poll, older adults cited a lack of awareness, lack of need, lack of comfort using the technology, and dislike of communicating about their health online as reasons for not setting up a patient portal.

But even at that time, only 26% said their health care provider didn't offer a patient portal. As more physicians have become affiliated with large health systems that have started offering a central portal system as part of their electronic medical record systems, it's likely that older adults will have more access than before.

Of course, the COVID-19 vaccination process is just one reason that setting up patient portal access could help older adults manage their health.

Among adults who had set up a patient portal account by the time of the 2018 poll, the most common use was to see test results (84%). Other common uses were requesting a prescription refill (43%), scheduling an appointment (37%), requesting reminders about upcoming appointments (34%), getting advice about a health problem (26%), updating insurance or contact information (22%), and requesting a referral (13%).

In the past year, patient portals have become increasingly important as the way to have a telemedicine visit, which allow people to have visits with their health providers from home.

The newly analyzed data come from a poll question asked in June 2020, soon after the rapid shift to telemedicine by many health systems amid the pandemic.

In August 2020 using data from that same poll, the National Poll on Healthy Aging reported that 26% of older adults had had at least one telehealth visit in the March through June period of 2020. This compared with just 4% who had ever had a telemedicine visit at the time the poll last asked about this topic, in May 2019.

Credit: 
Michigan Medicine - University of Michigan

Climate change is hurting children's diets, global study finds

image: A first-of-its-kind global study finds that higher temperatures are an equal or even greater contributor to child malnutrition and low quality diets than the traditional culprits of poverty, inadequate sanitation, and poor education.

The study is the largest investigation of the relationship between our changing climate and children's diet diversity to date.

The study examines diet diversity among 107,000 children 5 and under in 19 countries in Asia, Africa, and South America. Of the six regions examined-- five had significant reductions in diet diversity associated with higher temperatures.

Pictured: A farmer and child outside of Dodoma, Tanzania.

Image: 
C. Shubert (CCAFS)

A first-of-its-kind, international study of 107,000 children finds that higher temperatures are an equal or even greater contributor to child malnutrition and low quality diets than the traditional culprits of poverty, inadequate sanitation, and poor education.

The 19-nation study is the largest investigation of the relationship between our changing climate and children's diet diversity to date. It is believed to be the first study across multiple nations and continents of how both higher temperatures and rainfall--two key results of climate change--have impacted children's diet diversity.

"Certainly, future climate changes have been predicted to affect malnutrition, but it surprised us that higher temperatures are already showing an impact," said lead author Meredith Niles, an assistant professor of Nutrition and Food Sciences at the University of Vermont and a fellow at the university's Gund Institute for Environment.

Led by University of Vermont researchers, the study examines diet diversity among 107,000 children 5 and under in 19 countries in Asia, Africa, and South America, using 30 years of geo-coded temperature and precipitation data, and socioeconomic, ecological, and geographic data.

The study finds that the negative effects of climate--especially higher temperature--on diet diversity are greater in some regions than the positive effects of education, water and sanitation and poverty alleviation--all common global development tactics. The findings were published today in Environmental Research Letters.

Of the six regions examined--Asia; Central and South America; North, West, and Southeast Africa, five had significant reductions in diet diversity associated with higher temperatures.

Researchers focused on diet diversity, a metric developed by the United Nations to measure diet quality and micronutrient intake. Micronutrients, such as iron, folic acid, zinc, and vitamins A and D, are critical for child development. A lack of micronutrients is a cause of malnutrition, which affects one out of every three children under the age of five. Diet diversity is measured by counting the number of food groups eaten over a given time period.

On average, children in the study had eaten food from 3.2 food groups (out of 10)-- including meat and fish, legumes, dark leafy greens and cereal greens--in the previous 24 hours. By contrast, diet diversity in emerging economies or more affluent countries such as China have been more than double this average (6.8 for children 6 and under).

"Diet diversity was already low for this group," said UVM co-author Brendan Fisher. "These results suggest that, if we don't adapt, climate change could further erode a diet that already isn't meeting adequate child micronutrient levels."

Severe childhood malnutrition is a significant global challenge. According to the United Nations, 144 million children under age 5 were affected by stunting in 2019, an effect of chronic malnutrition. In 2019, 47 million children under 5 suffered from wasting, or acute undernutrition the UN says, a condition caused by limited nutrient intake and infection.

The study also found that higher precipitation, another potential effect of climate change in some regions, was associated with higher child diet diversity. In some cases, the effect of higher precipitation had a greater impact on child diet diversity than education, improved sanitation or greater forest cover.

"Higher rainfall in the future may provide important diet quality benefits in multiple ways, but it also depends on how that rain comes," said co-author Molly Brown of the University of Maryland. "If it's more erratic and intense, as is predicted with climate change, this may not hold true."

The study builds on UVM global research into how nature improves both children's health, their diets, and human well-being. The findings suggest that, in addition to addressing current needs, policy makers need to plan for improving diets across the most vulnerable in the future with a warming climate in mind.

"A warming climate has the potential undermine all the good that international development programs provide," said co-author Taylor Ricketts, Director of UVM's Gund Institute for Environment. "In fact, that is something we find again and again in this global research: continued environmental degradation has the potential to undermine the impressive global health gains of the last 50 years."

Credit: 
University of Vermont

Scientists discover the secret of Galápagos' rich ecosystem

image: A Galápagos Toroise

Image: 
Alexander Forryan

New research has unlocked the mystery of how the Galápagos Islands, a rocky, volcanic outcrop, with only modest rainfall and vegetation, is able to sustain its unique wildlife habitats.

The Galápagos archipelago, rising from the eastern equatorial Pacific Ocean some 900 kilometres off the South American mainland, is an iconic and globally significant biological hotspot. The islands are renowned for their unique wealth of endemic species, which inspired Charles Darwin's theory of evolution and today underpins one of the largest UNESCO World Heritage Sites and Marine Reserves on Earth.

Scientists have known for decades that the regional ecosystem is sustained by upwelling of cool, nutrient-rich deep waters, which fuel the growth of the phytoplankton upon which the entire ecosystem thrives.

Yet despite its critical life-supporting role, the upwelling's controlling factors had remained undetermined prior to this new study. Establishing these controls, and their climate sensitivity, is critical to assessing the resilience of the regional ecosystem against modern climatic change.

In this new research, published in Nature Scientific Reports, scientists from the University of Southampton, National Oceanography Centre and Universidad San Francisco de Quito in Ecuador used a realistic, high-resolution computer model to study the regional ocean circulation around the Galápagos Islands.

This model showed that the intensity of upwelling around the Galápagos is driven by local northward winds, which generate vigorous turbulence at upper-ocean fronts to the west of the islands. These fronts are areas of sharp lateral contrasts in ocean temperature, similar in character to atmospheric fronts in weather maps, but much smaller.

The turbulence drives upwelling of deep waters toward the ocean surface, thus providing the nutrients needed to sustain the Galápagos ecosystem.

Alex Forryan of the University of Southampton, who performed the research, said: "Our findings show that Galápagos upwelling is controlled by highly localised atmosphere-ocean interactions. There now needs to be a focus on these processes when monitoring how the islands' ecosystem is changing, and in mitigating the ecosystem's vulnerability to 21st -century climate change."

Professor Alberto Naveira Garabato, also of the University of Southampton, who led the project supporting the research, said: "This new knowledge of where and how the injection of deep-ocean nutrients to the Galapagos ecosystem happens is informing ongoing plans to expand the Galápagos Marine Reserve, and improve its management against the mounting pressures of climate change and human exploitation."

Credit: 
University of Southampton

Fast food restaurant proximity likely doesn't affect children's weight

A new paper in Q Open finds that the availability of fast food restaurants on the route between children's houses and their schools does not affect children's weight.

Reducing the rate of childhood obesity is a top public health priority in the United States where obesity rates are 18.4% for those ages 6-11 and 20.6% for those ages 12-19. Childhood obesity is a documented risk-factor for negative physical and mental health outcomes. Obese children are also more likely to become obese adults and suffer associated health problems.

Researchers have proposed that the accessibility of affordable healthy food options may be an important determinant of childhood weight. Many public health figures are concerned about the role of fast-food restaurants on food consumption and resulting obesity in children. Local governments in the United States have the power to influence children's food options through the zoning process. Several cities, including Austin, Texas, and New York, have considered banning fast-food restaurants near schools.

This article investigates the effect of fast-food availability on childhood weight outcomes by gender, race, and location. The researchers used a novel identification strategy based on changes in fast food exposure along the route between home and school that occur as students progress through the public school system and transition to different types of schools, e.g., from elementary schools to intermediate schools or from intermediate schools to high schools.

Researchers here used Arkansas student Body Mass Index, collected from 2004 to 2010, and matched it to home and school address through annual school registration records. Home address was used to geocode the location of student residences.

The researchers identified fast-food restaurants on the route between children's houses and their schools. Fast food restaurants included the major hamburger chains and drive-in restaurants (e.g. McDonalds, Burger King, Wendy's), dairy stores with large fast-food menus (e.g., Dairy Queen), take-out pizza establishments, quick-service taco places (e.g., Taco Bell), sandwich delicatessens (e.g., Subway, Quiznos), and fried chicken restaurants (e.g., KFC, Chick-Fil-A). The researchers excluded specialty stores such as ice-cream parlors not selling other fast foods (e.g., Baskin-Robbins), coffee shops (e.g. Starbucks), and donut shops (e.g. Krispy Kream).

Using a radius of one-half mile to define exposure near home and school, the mean total exposure level is 3.34 restaurants. The majority of children in the sample had zero exposure within 0.5 miles of home (69.6%). In contrast, 45.2% of children have at least one fast-food restaurant located within 0.5 miles of their school.

Researchers then measured changes in fast-food exposure as students changed schools as a result of a natural progression through the school system over time, for example, the change from elementary school to junior high school, and thus had different exposure to fast food restaurants. The researchers found that changes in exposure have no effect on BMI z- score.

For example, increasing fast-food exposure by three restaurants moving from 4th to 10th grade increased the mean change in BMI by .003, less than one percent (0.7%) of the standard deviation.

Ultimately the researchers find no meaningful association between fast-food exposure along
the route to school and BMI. This conclusion holds across different ages of children and for subsamples by gender, race, and ethnicity. The researchers also found no differences by income as measured by whether the child qualifies for free or reduced-price school lunches or between urban and rural children. These findings suggest that simple exposure to fast-food establishments in the commercial food environment was not a primary driver of excess childhood weight gain among children. While it is possible that fast food restaurants matter but their effects on BMI are longer-term, the researchers found no evidence that longer exposures as in the 4th to 8th grade transition differ meaningfully from the 4th to 6th or 6th to 8th grade transitions.

"Policies that place restrictions on actions of individuals and businesses are costly," said the paper's author, Michael R. Thomsen. " We see this with the response to Covid-19. Even when imposed with the most well-intentioned of objectives, people resist attempts to constrain their will. If governments are going to pursue a strategy that requires the investment of time and monetary resources to get a policy passed and enforced, it must be for tangible good, not simply a feeling of having done something. Although there is a strong correlation between the availability of fast-food and obesity, the evidence for a causal relationship remains weak. With limited political capital, policy fights over limiting access to fast-food may not be worth the public health returns."

Credit: 
Oxford University Press USA

How aerosols are formed

image: The experimental setup in an ETH Zurich laboratory.

Image: 
ETH Zurich / Ruth Signorell

Aerosols are suspensions of fine solid particles or liquid droplets in a gas. Clouds, for example, are aerosols because they consist of water droplets dispersed in the air. Such droplets are produced in a two-step process: first, a condensation nucleus forms, and then volatile molecules condense onto this nucleus, producing a droplet. Nuclei frequently consist of molecules different to those that condense onto them. In the case of clouds, the nuclei often contain sulphuric acids and organic substances. Water vapour from the atmosphere subsequently condenses onto these nuclei.

Scientists led by Ruth Signorell, Professor at the Department of Chemistry and Applied Biosciences, have now gained new insights into the first step of aerosol formation, nucleation. "Observations have shown that the volatile components can also influence the nucleation process," Signorell says, "but what was unclear was how this was happening at the molecular level." Previously it was impossible to observe the volatile components during nucleation in an experimental setting. Even in a famous CERN experiment on cloud formation, the "Cloud" experiment, certain volatile components could not be directly detected.

Volatile components detected for the first time

The ETH researchers developed an experiment aimed at the first microseconds of the nucleation process. In the experiment, the particles formed remain intact during this time and can be detected using mass spectrometry. The scientists looked at nucleation in various gas mixtures containing CO2 and for the first time, they were able to detect the volatile components as well - in this case, the CO2. The researchers could show that the volatile components were essential for the formation of nuclei and also accelerated this process.

An analysis of the experimental data revealed that this acceleration is the result of the volatile components catalysing the nucleation of other, less volatile components. They do this by forming short-lived, heterogeneous molecular aggregates, known as chaperon complexes. "Because temperature determines the volatility of gas components, it also plays a decisive role in these processes," Signorell explains.

One reason the new research results are interesting is that they improve the understanding of nucleation, its molecular mechanisms and speed, in order to properly account for it in models for, say, cloud formation in the atmosphere. In addition, the results should help to improve the efficiency of technical processes for producing aerosols - such as the use of rapid cooling to capture CO2 from natural gas.

Credit: 
ETH Zurich

Physical virology shows the dynamics of virus reproduction

video: This is a high-speed Atomic Force Microscope movie of the first steps of viral self-assembly. It shows how a hexamer at the edge of the growing lattice gradually forms from the single viral protein subunits.

Image: 
Wouter Roos, University of Groningen

The reproductive cycle of viruses requires self-assembly, maturation of virus particles and, after infection, the release of genetic material into a host cell. New physics-based technologies allow scientists to study the dynamics of this cycle and may eventually lead to new treatments. In his role as physical virologist, Wouter Roos, a physicist at the University of Groningen, together with two longtime colleagues, has written a review article on these new technologies, which was published in Nature Reviews Physics on 12 January.

'Physics has been used for a long time to study viruses,' says Roos. 'The laws of physics govern important events in their reproductive cycle.' Recent advances in physics-based techniques have made it possible to study self-assembly and other steps in the reproductive cycle of single virus particles and at sub-second time resolution. 'These new technologies allow us to see the dynamics of viruses,' Roos adds.

Energy

In 2010, he first published a review article on the physics aspects of virology with two of his colleagues. 'Back then, almost all of the research on viruses was relatively static, for example exerting pressure on a virus particle to see how it responded.' At that time, studies on dynamic processes, such as self-assembly, were performed in bulk, without the option to zoom in on individual particles. 'This has changed over the last couple of years and therefore, we thought it was time for another review.' This paper, 'Physics of Viral Dynamics', was co-authored by Robijn Bruinsma from the University of California in Los Angeles (USA) and Gijs Wuite from VU Amsterdam (the Netherlands).

Viruses hijack cells and force them to make the protein building blocks for new virus particles and to copy their genetic material (either RNA or DNA). This results in a cellular soup full of virus parts, which self-assemble to produce particles of encapsulated RNA or DNA. 'No external energy is required for this process. And even in vitro, most viruses will self-assemble quickly.' This process was traditionally studied in bulk material, averaging out the behaviour of large numbers of virus particles. 'So, we had no idea of the variance in the assembly of individual particles.'

Sub-second scans

Over the last few years, technologies have been developed to study these individual particles in real-time. One of those is fast Atomic Force Microscopy (AFM). An atomic force microscope scans surfaces with an atom-sized tip and is therefore able to map their topology. 'Recently, the scanning speed of AFM increased dramatically and now we can carry out sub-second scans of surfaces that measure less than 1 micrometre squared using High-Speed AFM,' says Roos, who uses an AFM himself. 'This allows us to see how virus subunits assemble on a surface. It is a very dynamic process, with building blocks attaching and releasing.'

Single-molecule fluorescence is also used to study viruses, for example, the attachment of viral proteins to DNA. 'Using optical tweezers, we hold two tiny beads on either end of a DNA molecule. When viral proteins bind to the DNA, this will coil up and bring the two beads closer together. This is visualized by fluorescent markers attached to the beads.' Alternatively, proteins with fluorescent markers can be observed while they attach to viral DNA or to other proteins. A third technology is to use an optical microscope to measure interference of light that is scattered by virus particles. These patterns reveal the structure of the particles during assembly.

Toughen up

Other steps in the virus cycle can also be studied. 'After they have self-assembled, particles need to toughen up to withstand conditions outside the host cell,' says Roos. Other modifications also occur, which prepare the particles to infect other cells. The dynamics of this maturation process are important for our understanding of how viruses work. 'And after infecting new cells, the virus particle has to come apart to release its genetic material.'

New technology is now revealing the physical dynamics of viruses. It allows scientists such as Roos and his colleagues to study how genetic material is incorporated and which physical principles guide this process. Most antiviral drugs disrupt the first steps in infection, such as the binding of virus particles to their host cells. Using this new dynamic information, we could develop drugs that block self-assembly or other important steps in the reproductive cycle of the virus.

Nanotechnology

Insight into the physics of virus particles is also important for their use in research, for example as building blocks in nanotechnology or as carriers for antigens in vaccines. Several of the leading COVID-19 vaccines use adenoviruses to deliver the gene for the SARS-CoV-2 spike protein to cells, which then express this gene and consequently generate an immune response. 'Understanding how the adenovirus comes together and falls apart could help to create more stable vaccines.'

Simple Science Summary

Viruses are very small particles and it is therefore difficult to study them directly. They are also very dynamic; for example, virus particles self-assemble inside infected cells. In recent years, technical improvements have made it possible to study the dynamics of single virus particles and see what exactly happens during their reproductive cycle. These results can help scientists to develop drugs that disrupt the self-assembly or other important steps in the virus cycle. Furthermore, they may help to stabilize viruses that are used to produce vaccines, such as the adenovirus-based coronavirus vaccines. A review of the different techniques to study viral dynamics has now been published in the journal Nature Reviews Physics by University of Groningen physicist Willem Roos and two of his colleagues.

Credit: 
University of Groningen

Imaging technique proves effective in measuring mitochondrial dysfunction in motor neuron disease (MND)

Non-invasive imaging technique called 31-phosphorus magnetic resonance spectroscopy used to measure mitochondrial function in patients with motor neuron disease (MND)

Evidence shows that mitochondria - often referred to as the cell's battery - are impaired in MND

This technique could be used to measure the effectiveness of future treatments for MND

Researchers from the Sheffield Institute for Translational Neuroscience (SITraN) have used a new imaging technique to measure the function of mitochondria in patients with motor neuron disease (MND).

The research, published today (13 January 2021) in the journal Brain could provide new ways to assess the effectiveness of treatments currently in development for MND.

Researchers used an advanced imaging technique called 31-phosphorus magnetic resonance spectroscopy to measure chemicals that are crucial to energy metabolism in the cell. The research was conducted on patients living with MND as well as age and gender matched healthy controls. The patient perceives the procedure as a standard MRI scan but researchers are able to gain a direct measurement of chemicals so that they can calculate a comprehensive picture of the energy status in patients with MND.

MND, or amyotrophic lateral sclerosis (ALS), as it is also known, is a disorder that affects the nerves - motor neurons - in the brain and spinal cord that form the connection between the nervous system and muscles to enable movement of the body. The messages from these nerves gradually stop reaching the muscles, leading them to weaken, stiffen and waste.

There are many barriers to developing effective treatments for MND as we don't yet fully understand how or why it develops in the first place. However, there is good evidence from laboratory data and disease models that the mitochondria - or powerhouses of the cell - may be impaired.

Lead author on the study, Dr Matilde Sassani from the University of Sheffield, explains: "It is important to have an effective technique to measure mitochondrial function in vivo in patients living with MND.

"In this study we found that phosphocreatine levels were depleted in the brain compared to healthy controls and, in the muscle, we found that inorganic phosphates were elevated in patients with MND. Both of these findings are consistent with mitochondrial dysfunction occurring in these people living with MND."

Dr Thomas Jenkins, senior author of the paper and Clinical Senior Lecturer at SITraN, said: "This research has the potential to impact the development of more effective treatments for MND. It appears to be a promising tool with potential to measure the effect of medications acting on mitochondrial function in people living with MND.

"Treatments that aim to rescue mitochondrial function in MND are being investigated in labs around the world. This non-invasive tool can demonstrate whether medications in development are successfully targeting mitochondria, which is an important step in selecting treatments to take through to clinical trials."

Future research aims to widen the scope of this study to include larger numbers of MND patients. As the mitochondria are also thought to be a factor in a range of other neurodegenerative diseases, there may be potential for this technique to be widened to different patient groups.

Credit: 
University of Sheffield

Scientists modeled protein behavior of archaeal viruses to crack protein folding mystery

image: Shown overlay comparison of PDB structure 2J6B (red) and its multi-soliton structure (blue).

Image: 
FEFU press office

Scientists from the Pacific Quantum Center of Far Eastern Federal University (FEFU) figured out how the AFV3-109 protein with slipknot structure folds and unfolds depending on temperature. The protein is typical for the viruses of the oldest single-celled organisms that can survive in the extreme conditions of underwater volcanic sources - archaea. The research outcome appears in PLOS ONE.

Using numerical methods and applying quantum field theory that is unique for the study of proteins, the FEFU scientists have probed into the folding topology (scheme) of the AFV3-109 protein featured with a slipknot. The research unfolded in several unexpected and intriguing results.

First, it turned out that the sliding knot of the AFV3-109 protein goes through an intermediate knot, which has the topology of a much more complex trefoil knot, a simplest non-trivial knot in mathematics.

Second, before folding of the slipknot is complete, it precedes by the swelling of the almost practically correctly folded AFV3-109 structure in a manner that the free end of the protein can pass into the loop of the knot.

Third, the correct protein structure formation is divided into stages. At the beginning solid secondary structures form, i.e. threads and spirals, and then they fold into a regular knot.

"The knotted structure of proteins makes them more durable and allows viruses, together with archaea, to withstand high temperatures. On the other hand, the presence of a knot makes the protein folding process nontrivial, because the protein cannot fold into the correct three-dimensional structure just by simple random movements of individual parts of the protein backbone. A lot of previous studies carried out by molecular dynamics methods have shown a low probability of such a knot formation, but in nature, this protein always forms a slipknot", says Dr. Alexander Molochkov, Head of the Pacific Quantum Center.

For the long AFV3-109 protein molecule that ties itself into a knot, the coordinated collective behavior of the molecule as a whole is necessary. One feels like someone is purposefully tying the molecule into a knot. Such behavior turns the protein into an essential model to study mechanisms of folding's complex topology formation. The recent remarkable advances in protein structure prediction by machine learning methods still do not reveal the nature of this structure's formation.

"In our work, we investigate the laws of symmetry that govern the behavior of a protein molecule. We managed to find out that local and chiral symmetry properties completely determine these complex processes and the non-trivial form of the protein", proceeds Alexander Molochkov. "This further confirms that every part of the protein is critical for the entire molecule to function properly. It also means that field theory is relevant for modeling the behavior of proteins that underlie all life."

Following a classical field theory, each atom's motion can be considered a part of a collective degree of freedom with a certain number of common coordinates, such as a kink or soliton. An example of such a soliton is a tsunami wave with its destructive power.

Therein a protein behaves as a whole akin tsunami. If one puts out a fragment of the protein, the entire molecule stops working correctly. The task of scientists is to detect which area to deactivate. That to be the key to understand the nature of many diseases triggered by protein misbehavior, including cancer, type 2 diabetes, infectious dementia syndrome (where proteins - prions cause dementia), and enveloped viruses, including the novel coronavirus, Ebola, and AIDS.

Previously, FEFU researchers modeled the WW-domain's behavior of the FBP28 protein and found out how the replacement of individual amino acids leads to the rearrangement of the protein's entire structure and the consequences of changes in specific amino acids in certain places in the molecular chains.

For the first time, FEFU scientists applied field theory to investigate proteins to predict the environment temperature and acidity-dependent changes in myoglobin structure. The paper explained the release of oxygen molecules when acidity at a certain site of myoglobin changes.

Credit: 
Far Eastern Federal University

BU researchers uncover viral small RNAs in mosquito cells

(Boston)--Researchers from Boston University School of Medicine (BUSM) provide a new genomics resource that details the small RNA transcriptomes (gene expression) of four bio-medically important mosquito species.

This is the first study to provide a platform for biologists to compare the characteristics of these small RNAs between these four mosquitoes as well as the most widely used insects for genetic experiments, the fruit fly, Drosophila. Although previous studies looked at each of the individual mosquito species separately, this study is the first to allow comparisons between all four species.

"Although mosquitoes are related to Drosophila, they have very different genomes. In addition, mosquitos bite humans for blood meals that allow them to reproduce and but unfortunately allows serious human pathogens like viruses to infect us and cause diseases like yellow fever virus, dengue fever virus, zika virus and eastern equine encephalitis virus," explained corresponding author Nelson Lau, PhD, associate professor of biochemistry at Boston University School of Medicine (BUSM).

The researchers obtained cell cultures and dissected samples of the mosquito species Anopheles gambiae, Culex quinquefasciatus, Aedes aegypti and Aedes albopictus. They extracted and purified the small RNA molecules, created libraries for high-throughput sequencing, and then developed a special bioinformatics platform to provide thorough genomic analysis of these small RNAs. They provide all this analysis in a database website for the public to access at https://laulab.bu.edu/msrg/.

The four mosquito species have global impacts on human health. Anopheles is the major vector for the parasite causing malaria, but is not known to transmit many viruses. In contrast, Culex and Aedes mosquitoes are well known to pass viruses between humans during mosquito bites, but it is still unknown why there is this difference between mosquito species for this capacity to spread viruses.

According to the researchers this study will allow for better biochemical studies in mosquito cells. "If we can find weaknesses in the small RNA pathways of mosquitoes to make them more intolerant of viruses, perhaps they won't be so able to pass the virus from biting one human to the next human victim."

Credit: 
Boston University School of Medicine

KU studies show breakfast can improve basketball shooting performance

LAWRENCE -- Parents around the world have long told us that breakfast is the most important meal of the day. Soon, basketball coaches may join them.

Researchers at the University of Kansas have published a study showing that eating breakfast can improve a basketball player's shooting performance, sometimes by significant margins. The study, along with one showing that lower body strength and power can predict professional basketball potential, is part of a larger body of work to better understand the science of what makes an elite athlete.

Breakfast and better basketball shooting

Dimitrije Cabarkapa left his native Novi Sad, Serbia, to play basketball at James Madison University. Never a fan of 6 a.m. workouts, he was discussing whether the provided breakfast helped performance with his teammates. While he felt it was important, others argued it either didn't make a difference or made their games worse. When he came to KU to seek his doctorate in exercise physiology, he decided to take a more scientific approach to the question.

Cabarkapa and colleagues recruited a cohort of 18 young players with high-level basketball ability, some having played professionally, some in the collegiate ranks and all with experience. Two groups were formed, one of which had breakfast before taking part in shooting drills, while another did not have an early meal before the same drills. After one week, the groups switched, and the tests were repeated. Results showed a statistically significant improvement in free throw shooting percentage and practically significant improvement in others.

The study, co-written with Andrew Fry, professor of health, sport & exercise science and director of the Jayhawk Athletic Performance Laboratory at KU, and Michael Deane and Jeremy Akers of James Madison University, was published in the journal Physical Education and Sport.

The participants took part in a week of drills in which they took a series of two-point and three-point shots from designated spots on a basketball floor as well as free throws. After each week of shooting after breakfast and without, their shooting performances were tabulated.

"We chose shooting because you need high cognitive involvement to put the ball in the little orange bucket. You also need energy to physically push through," Cabarkapa said. "We wanted to study a possible relationship between breakfast consumption and basketball shooting influenced by anticipated improvements in mental and physical performance. A lot of research has shown the connection between breakfast and diet quality, but as far as we know, none has looked at the relation between breakfast and basketball performance."

Results showed that while nearly all shooting categories improved when participants had breakfast, free throw percentage saw the highest difference. Others, such as three-point attempts, overall shots made and two-point shot percentage had practically significant, though not statistically significant, improvements. However, those close to the game know an additional made shot here and there can make a difference.

"If you come to somebody and tell them you can improve their shooting by 6%, any coach or player is going to ask how," Cabarkapa said. "This shows having breakfast is a simple way to do that. Even slightly improved shooting performance can influence the outcome of a game."

In addition to data on shooting performance, researchers collected information on participants' diets, including calories, carbohydrates, protein and fat intake during breakfast and non-breakfast weeks. During the first session, subjects were provided information on nutritional values of various foods and encouraged to eat nutritionally balanced breakfasts. They logged information on their diets throughout the testing period, including food and liquids they consumed, amounts and how foods were prepared.

Researchers said they hope to continue analyzing the connections between breakfast and basketball performance. Cabarkapa, who regularly consumed breakfast in his playing days, including when his James Madison team competed in the NCAA tournament, said providing subjects food and testing over longer periods of time could reveal more about breakfast's influence on performance. Meanwhile, even small improvements shown from this study suggest the value of nutrition in making another free throw or two per game, or making several more shots over the course of a season.

"Athletes are always looking to improve performance. Always looking for a competitive edge," he said. "I always say there are three pillars of athletic performance: Strength and conditioning, nutrition and sport psychology. People often talk about taking supplements or other ergogenic aids to improve performance but often forget about basic stuff like well-balanced diet."

Lower body strength, power and professional potential

Professional scouts examine the aforementioned pillar of strength and conditioning when evaluating which players might succeed in the ranks of professional basketball. Yet, there is still disagreement among players, trainers and coaches as to exactly which types of strength are most beneficial to players. Lower body strength that enables players to jump higher, run faster and make quick lateral movements is often analyzed by scouts, so KU researchers decided to measure performance in the area among high level players to see if those who went on to play professionally indeed had greater performance in that area.

After analyzing seven years of data from Division 1 men's college basketball players, those who played professionally in the NBA, European or other professional leagues consistently scored higher in lower body strength and power measures.

Cabarkapa and Fry co-wrote the study with Michael Lane of Eastern Kentucky University; Andrea Hudy of the University of Texas and former KU strength and conditioning coach; Patricia Dietz of Wartburg College; Glenn Cain of Rutgers University; and Matthew Andre of George Mason University. The study was published in the journal Sports Science and Health.

Researchers graphed the power and speed of players using digital devices and 3D cameras while weight training. Over the course of seven years, nearly three dozen of the participants finished playing college basketball as "one and done" top-level NBA draft choices, while some were draftees after two or more years, some graduated and played professionally, and others completed their eligibility and did not play professionally.

"Essentially we were having them do what's called a speed squat," Fry said. "When they hit the parallel position, they stood up as quickly as possible. A device measured the speed of the bar and their power. They did that at various weight loads, and we measured their average power."

The results showed that players who went on to play in the NBA had significantly higher performance in all variables, including one-repetition squat strength and maximum squat bar power, than those who played in other professional leagues. Those players had higher scores, in turn, than those who did not play professionally. When adjusted for body weight, there was no difference between groups observed, meaning body size was also an important factor.

The findings show that high levels of lower body strength and power are instrumental to success in professional basketball. While scouts and general managers do consider strength when deciding which players to draft or sign, the NBA combine does not measure barbell squat strength or similar measures when evaluating players, the authors said. The findings add to a large body of literature showing strong relationships between weight room performance and sport performance.

"In essence, the more power you can generate, the greater chance you had of going pro. The conclusion of our study is lower body strength and power are highly related to a greater level of play," Cabarkapa said.

The researchers emphasized that the findings should not be taken to mean basketball players should lift as much weight as they possibly can in order to go pro, but that coaches and trainers should develop programs to optimize players' lower body strength and power in order to both improve their performance and help their future prospects. In turn, professional talent evaluators would do well to consider this specific area of strength and power as a variable in making decisions on players' potential.

"The question is not 'what's the maximum amount of strength and power I can get' but 'what's the optimum amount of strength and power for a basketball player,'" Fry said. "It's not the only factor, but there is certainly a relationship between lower body strength and power and on-the-court performance."

Credit: 
University of Kansas

GSA publishes seven new research articles on COVID-19 and aging

The Gerontological Society of America's highly cited, peer-reviewed journals are continuing to publish scientific articles on COVID-19. The following were published between December 5 and January 6; all are free to access:

Reactive, Agentic, Apathetic, or Challenged? Aging, Emotion, and Coping During the COVID-19 Pandemic: Research article in The Gerontologist by Nathaniel A Young, MA, Christian E. Waugh, PhD, Alyssa R. Minton, MA, Susan T. Charles, PhD, Claudia M. Haase, PhD, and Joseph A. Mikels, PhD
#MoreThanAVisitor: Families as “Essential” Care Partners during COVID-19: Forum article in The Gerontologist by Candace L. Kemp, PhD
The COVID-19 Pandemic and Psychosocial Outcomes across Age through the Stress and Coping Framework: Research article in The Gerontologist by Jillian Minahan, MA, Francesca Falzarano, PhD, Neshat Yazdani, MA, and Karen L. Siedlecki, PhD
Age Differences in COVID-19 Related Stress and Social Ties during the COVID-19 Pandemic: Implications for Well-being: Research article in The Gerontologist by Kira S. Birditt, PhD, Angela Turkelson, MS, Karen L. Fingerman, PhD, Courtney A. Polenick, PhD, and Akari Oya, BA
Transforming Aging Services: Area Agencies on Aging and the COVID-19 Response: Forum article in The Gerontologist by Haley B. Gallo, BS, and Kathleen H. Wilber, PhD
Obtaining Information from Different Sources Matters During the COVID-19 Pandemic: Research article in The Gerontologist by Li Chu, PhD, Helene H. Fung, PhD, Dwight C. K. Tse, PhD, Vivian H. L. Tsang, MPhil, Hanyu Zhang, BS, and Chunyan Mai, MA
The effects of the COVID-19 pandemic on the lived experience of diverse older adults living alone with cognitive impairment: Research article in The Gerontologist by Elena Portacolone, MPH, MBA, PhD, Anna Chodos, MD, MPH, Jodi Halpern, MD, PhD, Kenneth E. Covinsky, MD, MPH, Sahru Keiser, MPH, Jennifer Fung, BS, Elizabeth Rivera, MS, Thi Tran, BA, Camilla Bykhovsky, BS, and Julene K. Johnson, PhD

Credit: 
The Gerontological Society of America

Aggressive video games: Effects on mental health and behaviors in young people

image: Explores the psychological and social issues surrounding the Internet and interactive technologies

Image: 
Mary Ann Liebert, Inc., publishers

New Rochelle, NY, January 13, 2021--Aggressive video games are not a risk factor for mental health problems, according to a new study of more than 3,000 youth. This study is part of a special issue on the effects of violent video games published in the peer-reviewed journal Cyberpsychology, Behavior, and Social Networking. Click here to read the issue now.

Christopher Ferguson, PhD, Stetson University, and C.K. John Wang, PhD, Nanyang Technological University, examined whether early exposure to aggressive games was predictive of anxiety depression, somatic symptoms, or attention deficit hyperactivity disorder 2 years later.

In an editorial entitled, "Effects of Violent Video Games: 50 Years On, Where Are We Now?" Guest Editors of the special issue, Simon Goodson, PhD and Kirstie Turner, PhD, University of Huddersfield, state: "The aim of this special issue is to present empirical findings based upon meticulous research in order to provide a more informed resource for the debate of the effects of playing violent video games."

Manuel Ibáñez, , PhD, Universitat Jaume I, and coauthors examined the role of violent video game exposure, personality, and deviant peers in aggressive behaviors among adolescents. They found that aggressive behavior was predicted by having deviant peers and specific personality traits, especially low agreeableness. Violent video game exposure had no long-term effects on aggressive behaviors.

"Video games have been criticized from the moment they came into being and, like with most other new technologies, we've discovered there are benefits as well as shortcomings to consider. My hope is that by publishing this special issue, highlighting cutting-edge research with objective data, we may come to better understand both the promise and peril of videogames," says Editor-in-Chief Brenda K. Wiederhold, PhD, MBA, BCB, BCN, Interactive Media Institute, San Diego, California and Virtual Reality Medical Institute, Brussels, Belgium.

Credit: 
Mary Ann Liebert, Inc./Genetic Engineering News

Study: Many summer camps don't require childhood immunizations

While most children need to show immunization records to attend school, the same may not be true for camps, a new study suggests.

Nearly half of summer camps surveyed by researchers didn't have official policies requiring campers be vaccinated, according to findings led by Michigan Medicine C.S. Mott Children's Hospital in JAMA Pediatrics.

Of 378 camps represented, just 174 reportedly had immunization policies for campers and 133 (39%) mandated staffers be vaccinated. A little more than half of camps also allowed unvaccinated children with nonmedical exemptions to attend programs.

"While all states require immunizations for children attending public schools, most don't have the same mandates for summer camps," says lead author Carissa Bunke, M.D., of Mott Children's Hospital. "Campers are often in close contact and sharing common spaces, increasing risk for illness outbreaks.

"As we think about reducing the spread of infectious diseases, children in camps may be an important population to consider."

Researchers surveyed 710 respondents representing camps, including owners, directors, nurses, office staff and physicians. While the majority of camp leadership agreed that campers should be fully immunized prior to attending camps, policies didn't always reflect these views.

Nearly 14 million children attend camp every year. Multiple vaccine-preventable outbreaks have been reported over the last decade, including a 2009 mumps outbreak traced to a New York camp.

The American Academy of Pediatrics policy recommends that camps require all campers, staff and volunteers to receive and provide documentation of all age-appropriate vaccines. The AAP also states that camps should eliminate nonmedical exemptions.

The guidelines were released in 2019 as the number of measles cases reported in the United States rose to the highest case count since 1992 and since the disease was declared eliminated in 2000.

"While 100% vaccination rates may not always be possible, camps have a responsibility to take all measures to protect their campers and staff from vaccine-preventable diseases," says senior author Andrew Hashikawa, M.D., a pediatric emergency medicine physician at C.S. Mott Children's Hospital.

"Routine vaccination is critical to both individual and public health. With the rise in vaccine preventable outbreaks, future efforts to reduce the spread of communicable diseases should address these findings."

Credit: 
Michigan Medicine - University of Michigan