Culture

With cases increasing in the UK and elsewhere, and winter approaching, there is an urgent need for reliable models that predict the likely course of Covid-19, to support decisions about shielding, hospital admission, treatment, and vaccinations.

The risk prediction tool (known as QCOVID) uses readily available information about people, such as their age, ethnicity and whether they have certain pre-existing conditions (comorbidities) to help identify individuals at highest risk of developing severe illness. It is designed to be applied across the general adult population in the UK.

The tool provides nuanced information on people's risk of serious illness due to Covid-19 and is designed for use by clinicians with patients to reach a shared understanding of risk.

The tool will need to be updated regularly as the pandemic evolves and its performance closely monitored.

Some previous risk prediction models have been developed. They have been identified as having a high risk of bias, raising concerns that these models may be unreliable when applied in practice.

The UK-wide research group set out to develop and validate a population-based prediction model to estimate the overall risks of becoming infected with and subsequently being admitted to hospital or dying from Covid-19. Steps were taken to mitigate known sources of bias.

Their findings are based on data from more than 8 million patients aged 19-100 years at 1,205 general practices in England, linked to Covid-19 test results and hospital and death registry data.

Data from 6 million patients were used to develop the model over a 97 day period (24 January to 30 April 2020), and a further 2.2 million patients to validate its performance over two separate time periods (24 January to 30 April 2020 and 1 May to 30 June 2020) during the first wave of the pandemic.

To develop the model, known factors such as age, ethnicity, deprivation, body mass index, and a range of comorbidities were used to estimate the probability and timing of hospital admission or death from Covid-19.

Over the study period, 4,384 deaths from Covid-19 occurred in the development group, 1,782 in the first validation time period and 621 in the second validation time period.

The model performed well, predicting 73% and 74% of the variation in time to death from Covid-19 in men and women, respectively.

People in the top 5% for predicted risk of death, accounted for 76% of Covid-19 deaths within the 97-day study period. People in the top 20% for predicted risk of death accounted for 94% of Covid-19 deaths.

The researchers point out that the model aims to provide predictions of risk - it does not aim to provide explanations of which individual factors causally affect risk and the results should not be interpreted in this way.

The absolute risks obtained from the model will change over time, in line with the prevailing Covid-19 infection rate and the extent of social distancing measures in place, so these should also be interpreted with caution. However, the ordering of individuals in terms of their risk is expected to remain relatively stable over time, so that those at highest risk can be identified.

The researchers say that QCOVID represents a robust risk prediction model that has the potential to support public health policy, from enabling shared decisions to mitigate health and workplace risks to targeted recruitment for clinical trials and prioritisation for vaccination.

The model can also be recalibrated for different time periods and has the potential to be updated regularly as the pandemic evolves.

Although QCOVID has been specifically designed to inform UK health policy and interventions to manage Covid-19 related risks, it has international potential, subject to local validation, they conclude.

In a linked editorial, researchers at the University of Manchester agree that QCOVID and the ISARIC (International Severe Acute Respiratory and emerging Infection Consortium) 4C (Coronavirus Clinical Characterisation Consortium) Mortality Score represent steps forward in the quality of Covid-19 prognosis models, but say care must be taken when interpreting the predictions generated by these models.

Given the rapidly changing nature of the disease and its management, they also emphasise the need to update these models regularly and closely monitor their performance over time and space.

They acknowledge that improved data on incident cases of Covid-19 "will allow greater granularity in prediction" and say with these caveats, "we support the continued validation and impact assessment of these models."

WASHINGTON, October 20, 2020 -- Contagion processes, such as opinion formation or disease spread, can reach a tipping point, where the contagion either rapidly spreads or dies out. When modeling these processes, it is difficult to capture this complex transition, making the conditions that affect the tipping point a challenge to uncover.

In the journal Chaos, from AIP Publishing, Nicholas Landry and Juan G. Restrepo, from the University of Colorado Boulder, studied the parameters of these transitions by including three-person group interactions in a contagion model called the susceptible-infected-susceptible model.

In this model, an infected person who recovers from an infection can be reinfected. It is often used to understand the propagation of things like the flu but does not typically consider interactions between more than two people.

"With a traditional network SIS model, when you increase the infectivity of an idea or a disease, you don't see the explosive transitions that you often see in the real world," Landry said. "Including group interactions in addition to individual interactions has a profound effect on the system or population dynamics" and can lead to tipping point behavior.

Once the rate of infection or information transfer between individuals passes a critical point, the fraction of infected people explosively jumps to an epidemic for high enough group infectivity. More surprisingly, if the rate of infection decreases after this jump, the infected fraction does not immediately decrease. It remains an epidemic past that same critical point before moving back down to a healthy equilibrium.

This results in a loop region in which there may or may not be high levels of infection, depending on how many people are infected initially. How these group interactions are distributed affects the critical point at which an explosive transition occurs.

The authors also studied how variability in the group connections -- for example, whether people with more friends also participate in more group interactions -- changes the likelihood of tipping point behavior. They explain the emergence of this explosive behavior as the interplay between individual interactions and group interactions. Depending on which mechanism dominates, the system may exhibit an explosive transition.

Additional parameters can be added to the model to tune it for different processes and better understand how much of an individual's social network must be infected for a virus or information to spread.

The work is currently theoretical, but the researchers have plans to apply the model to actual data from physical networks and consider other structural characteristics that real-world networks exhibit.

HAMILTON, ON, Oct. 20, 2020 -- When COVID-19 attacks, the immune system produces a cytokine, or protein, called Interleukin-6 (IL-6), whose concentrations can offer vital information about a patient's level and stage of infection.

But measuring the critical marker has been extremely challenging, given its nearly undetectable presence in the biological stew that makes up human blood. Existing technology has not been accurate or sensitive enough to measure concentrations of IL-6 well enough to be reliable, especially in low concentrations.

Now researchers at McMaster University and SQI Diagnostics have created a surface that repels every other element of human blood except the critical cytokine, opening a timely window for understanding the progress of COVID-19 in individual patients.

The McMaster researchers are working to adapt the technology to the Toronto company's existing testing platforms, in the hope of moving it into clinical use as soon as possible. The same biosensing technology can also be used to measure other infectious and non-infectious diseases, including some cancers.

The innovative surface coating is made to repel every component of blood and other complex fluids such as urine, but is dotted with microscopic islands of molecules that attract IL-6, making it possible to detect and measure IL-6 with unprecedented accuracy and sensitivity, at concentrations as low as 0.5 picograms per mL - or one half of one trillionth of a gram per mL - making it far more sensitive than existing technology.

It is the latest application of smart-surface technology to emerge from the laboratory of Tohid Didar, a mechanical engineering professor at McMaster who has recently been involved in projects to create a reactive tag for food packaging that indicates the presence of harmful pathogens, a form of wrap that can repel antimicrobial-resistant bacteria and a coating for surgical implants that can repel infection while attracting cells that promote integration with surrounding tissue.

"There are so many possibilities for these smart surfaces. We can create them to repel everything, or we can design them to interact in many beneficial ways," Didar says. "Here, we're looking for something, and only that one thing, and this allows us to separate it from everything else in a very complex environment."

The new smart surface for detecting IL-6 can be printed inexpensively onto the inside of test tubes and onto other platforms used in diagnostic testing. After a sample of blood is exposed to the surface and removed, the captured IL-6 can readily be measured.

"The technology was challenging to create, but it is easy to use in many applications, including in testing kits that already exist," says co-author Amid Shakeri, a PhD student in Didar's lab. "I'm very happy that we can actually be involved in something that could be important for humankind, and I'm hopeful we can get this into clinical settings very soon."

"Our partnership with McMaster University has opened up an innovative pathway to a low-cost manufacturing design to enable affordable and accurate diagnostics, especially for testing in the COVID-19 pandemic" said Dr. Eric Brouwer, Chief Scientific Officer of SQI Diagnostics.

A paper introducing the technology is published today in the journal Small.

Cannabinoids have a strong influence on how our brains work and how we behave. Many people are only aware of the recreational aspect of cannabinoids. But in fact these molecules naturally exist in our brains where they participate in various intrinsic processes.

Altered cannabinoid signalling, for instance due to chronic use of marijuana, results in a range of impairments. Similarly, mice lacking cannabinoid receptors exhibit reduced activity levels, as well as deficits in learning and memory.

How do cannabinoids exact their effect on learning? A team led by Megan Carey, a principal investigator at the Champalimaud Centre for the Unknown in Portugal, and Catarina Albergaria, a postdoctoral researcher in the lab, decided to tap into this question by investigating the brain mechanisms involved in a classical learning task called eyeblink conditioning.

The immediate suspect

In eyeblink conditioning, subjects learn to associate the appearance of a sensory stimulus, for example a flash of light, with a subsequent delivery of an airpuff to the eye. Once learned, the subject - in this case a mouse - closes its eyes when the light appears to avoid the airpuff. "It's just like Pavlov's dog and the bell," says Albergaria.

Previous studies had established that this form of learning takes place in a brain structure called the cerebellum, and that it was impaired by altered cannabinoid signaling in both humans and mice. To study the role of cannabinoids in learning, the team used mutant mice lacking cannabinoid receptors, which show impaired eyeblink conditioning.

Why are these mice impaired? When they started, the researchers had an immediate suspect in mind. "Many studies support the idea that cannabinoids mediate neural plasticity, or experience-dependent changes in the connections between neurons," Carey explains. "We therefore first hypothesized that interfering with this process was what was driving the impairments in learning."

But like a good mystery novel, the immediate suspect turned out to be the wrong one. What was the real culprit? "In a study we published two years ago, we found that the more mice ran, the better they learned", Albergaria explains. The team began to suspect that the difference in learning might instead be due to the reduced activity levels of the mutant mice.

Spotlight on behavioural state

"We wondered whether the mutant mice weren't learning as well simply because they weren't active enough," Albergaria recalls. Today in the journal eLife, the team reports that the altered behavioral state of the mutants fully accounts for their impaired eyeblink conditioning. When the researchers placed the mice on a motorised treadmill that ensured that the mutants walked as much as normal mice, the results were striking: learning was completely restored.

The team also found that other cerebellar behaviors, locomotor coordination and learning, were normal in the cannabinoid mutants. Further, eyeblink conditioning was fully intact in mice that lacked cannabinoid receptors specifically within the cerebellum. "These experiments further supported our hypothesis that disrupted cannabinoid signaling was impairing learning by altering behavioral state, and not through direct effects on neural plasticity in the cerebellum," says Carey.

"There is a growing body of evidence that behavioural state profoundly influences brain function," says Carey. "Our study highlights the need to consider behavioral state as a powerful independent means through which individual genes contribute to complex behaviors."

"We were able to overcome a learning deficit associated with a genetic mutation with a purely behavioral intervention," adds Albergaria, suggesting a potential real-world consequence for these findings.

COLUMBUS, Ohio - A blend of racial prejudice, poor coping and partisan media viewing were found in Americans who stigmatized people of Asian descent during the COVID-19 pandemic, according to a new study.

But it was prejudice against Asian Americans that was most strongly linked to beliefs that Asians were responsible for the pandemic and most at risk for spreading it, results showed.

"It was striking that this general prejudice against Asian Americans appeared to play a powerful role in the stigmatization of this group in the specific context of COVID-19," said Hyunyi Cho, lead author of the study and professor of communication at The Ohio State University.

Findings were published online recently in the journal Ethnicity and Health.

The study comes in the wake of other evidence of prejudice against Asian Americans linked to COVID-19, a virus that was first identified in the Wuhan province of China. An April poll of Americans found that one-third had seen someone blaming Asian people for the pandemic.

"We wanted to see what could explain people of Asian descent being stigmatized for this virus," Cho said.

The researchers conducted a nationwide survey of 842 American adults between May 11 and May 19.

Participants were asked a variety of questions about COVID-19 and how they have been impacted and coped with the pandemic's effects, media use, their views of Asian Americans, and other related issues.

Overall, stereotypical racial beliefs about Asians and envy about the success of some Asian Americans in society were most linked to stigmatization.

"It turned out that the stereotypes and beliefs that people already had about Asian Americans were more powerful in predicting stigmatization than other factors we studied," said Wenbo Li, study co-author and doctoral candidate in communication at Ohio State.

"That is what was most surprising to me."

But other factors did play a role, such as how people were coping with the pandemic.

People who reported higher levels of fear about COVID-19 were more likely to stigmatize. The same went for those who felt most harmed by the pandemic and also reported lower levels of ability to deal with the crisis.

As in many issues in the United States today, ideology played a role in stigmatization.

One example was where people got their news. Findings showed that people who reported more viewing of COVID-19 news on Fox News and social media outlets were more likely to blame Asian Americans and see them as a disease risk than those who got their news from CNN or MSNBC and didn't consume as much social media.

In addition, people who believed the Trump administration was doing a good job responding to the pandemic crisis were more likely to report prejudicial views about Asian Americans.

"We saw evidence in our results that stigmatization of Asian Americans because of COVID-19 can have a political and ideological aspect," Cho said.

But some findings suggested ways to help reduce the stigmatization aimed at people of Asian descent, Cho and Li said.

For example, results showed that people who reported watching more foreign language movies showed less prejudice.

"Being exposed to other cultures, even through media like movies and TV, can help mitigate stereotypes," Cho said.

Most importantly, lower stigmatization was found in people who reported higher levels of what researchers call "collective efficacy." People high in collective efficacy strongly agreed with statements like "I feel that Americans can work together to effectively overcome the current COVID-19 crisis."

"Finding ways to foster collective efficacy can be an antidote to divisive communication on partisan cable television and social media," Li said.

The researchers said they believe this study has implications beyond Asian Americans and COVID-19.

"It is Asian Americans who are targeted in COVID-19. But in another crisis, it may be a different group," Cho said.

"It is about how people make sense of crises like this pandemic and how biases and prejudices can be exacerbated in situations like this."

Programmes to reduce dementia risk by targeting smoking, high blood pressure and hearing loss are likely to be cost-effective and cost saving by reducing dementia rates by 8.5%, finds a new study by UCL and LSE researchers.

The modelling study, published in The Lancet Healthy Longevity, found that the benefits would outweigh the costs of such programmes, and could save £1.86 billion each year in England.

Lead author Dr Naaheed Mukadam (UCL Psychiatry and Camden and Islington NHS Foundation Trust) said: "It is becoming increasingly clear that dementia can be prevented in many cases by addressing various health factors throughout the lifespan. As the number of people with dementia is expected to increase to 131 million worldwide by 2050, there is an urgent need to develop evidence-based interventions to prevent dementia, or delay it to enable more years of healthy life.

"Here, we have found that dementia prevention strategies can be cost-effective and cost saving, and should be implemented to reduce the societal burden of dementia."

The findings are based on extensive evidence, including from studies led by this study's researchers, finding that 12 risk factors can be modified across the life course to prevent 40% of dementia cases.

For the present study, the team reviewed evidence to find effective interventions for individuals targeting some of the dementia risk factors. The interventions included nicotine gum to help older adults quit smoking, medication to treat high blood pressure in mid-life, and hearing aids for people with moderate hearing loss in mid-life.

The researchers found that the three interventions combined would cost £1.08 billion annually in England, while reducing social care costs of dementia by £866 million and family care costs by £1.05 billion. The NHS and social care cost savings from dementia prevention would outweigh the costs of the smoking cessation and hearing loss interventions, while all three interventions would meet cost-effectiveness standards set out by the National Institute for Health and Care Excellence (NICE), as measured by cost per quality-adjusted life-year.

The model considered how well each intervention controlled each factor to reduce dementia risk, and accounted for the clustering of dementia risk factors (as many people are affected by more than one risk factor).

While this study focused on England, the researchers say their findings could likely apply similarly to other countries considering implementing dementia prevention strategies.

Senior author Professor Gill Livingston (UCL Psychiatry and Camden and Islington NHS Foundation Trust) said: "We have found that there's a strong case for implementing dementia prevention programmes. They are cost-saving for their impact on reducing dementia rates alone, without even factoring in the additional benefits in reducing other health issues such as stroke or heart disease."

The study was funded by the Economic and Social Research Council and was a collaboration between researchers at UCL and the London School of Economics and Political Science (LSE).

Fiona Carragher, Director of Research at Alzheimer's Society that funded the lead author said: "The evidence shows it's a no-brainer to invest in programmes to stop smoking, manage blood pressure and treat hearing loss, particularly given the cost of dementia to the economy is set to skyrocket as numbers of people with the condition increase. There isn't a fail-safe way to prevent dementia later in life but taking steps to reduce our risk has the potential to buck this worrying trend and give families the chance to have more precious, healthy years together.

"We look to the Government to act on these findings by making sure everyone knows what steps they can take to reduce their risk of dementia, and at the same time honour their commitment to double dementia research funding so we can continue this life-changing work."

Games and the very act of playing have been around since before the cradle of human civilization. However, games have constantly evolved over time, with various rulesets and modes of play falling in and out of favor throughout history. In turn, this implies that people at different times enjoyed different aspects of each game, which may constitute a vivid reflection of the cultural tendencies of each era. Unfortunately, the attractiveness of games is tied to human psychology, and finding objective evidence in topics related to the realm of the human mind is a difficult task. Could there possibly be a way to quantify universal characteristics of games so as to put them under rigorous mathematical analysis?

Professor Hiroyuki Iida, vice president and trustee of the Japan Advanced Institute of Science and Technology (JAIST), thinks that there is. Under his guidance, the Iida laboratory has put much effort into developing theories and models that explain, using concepts from mathematics and psychology, what players enjoy about different games and why they feel motivated to play. Now, in their most recent study published in IEEE Access, scientists at JAIST have developed a novel approach to quantify the psychological appeal of games from a perspective analogous to the basic laws of motion in physics.

Ms Kang Xiaohan, Ph.D. student and lead author of the study, explains that their research is based on a combination of game refinement theory, reinforcement schedules and 'motion in mind.' Game refinement theory is a methodology for assessing the enjoyment and entertainment value of a game based on variables such as uncertainty, match duration and difficulty. On the other hand, reinforcement schedules are a concept widely studied in psychology that explains how rewards and punishments (and their frequency) motivate specific human behaviors. In this case, a 'reward' in the psychological sense can be winning a game in a given match. Finally, "motion in mind" is a novel theory pioneered at Iida laboratory, which proposes an analogy between physical measures of motion (such as potential energy, force and momentum) and game-related measures perceived by players, including pace of the game, effort required to progress, and randomness.

One key measure in the model of motion in mind is the acceleration or 'gravity in the mind,' in analogy with the earth's gravitational acceleration. In sufficiently refined games, the model establishes a relationship between the effort that the player has to make to advance and the degree of challenge a game represents. The scientists calculated the gravity associated with a wide variety of games as they evolved through history, including classic board games like Chinese Go, Chess and Shogi, popular sports like soccer, tennis and basketball, and videogames, such as fighting games and strategy games.

Surprisingly, they found that the value of gravity in the mind changed, for each type of game, in sync with historical and cultural trends (Figure 1). For example, whereas people living 4000 years ago valued slow-paced games like ancient Go with a long period between rewards, the medieval and industrial era favored more aggressive and mid-paced games like Chess and Shogi (Figure 2). Similar trends were also found for various sports and videogames of the modern era. Excited about the results, Ms Xiaohan comments, "The gravity in the mind seems to be a good indicator of the core culture of people from a specific era or time. We can analyze how it changes to gain insight into people's cultural tendencies based on the type of playing experience they seek and their relative comfort."

The methodology and framework adopted in this study can be equally useful in other contexts where effort and motivation are critical factors, such as gamified activities, education and rehabilitation. It can also be used to analyze the nature of a given game or task so as to identify the psychological requirements for it, as well as the profiles of people that would be most comfortable or satisfied with it. In this regard, Prof Iida concludes, "We think the perspective of game-related research could shift naturally from the psychological realms to a more physical realm, making the generally complicated abstractions of the mind easier to understand." One thing is certain: as our understanding of the appeal of games increases, so does our understanding of ourselves and our history.

Which political parties have the most ambitious climate and energy policies? The answer, according to a new study, is surprising. In Germany, France, Spain and Italy, parties across the political spectrum, from the Greens to the Liberals, show a similar level of ambition on this score. However, researchers have also identified a major impediment to the energy transition: none of the investigated parties has a convincing idea for a technology mix that would ensure grid stability despite weather-related fluctuations in wind and solar energy.

The researchers analysed climate policies in the EU's four largest electricity markets. In the case of Germany and Spain, representative citizen polls were also considered in the investigation. As lead author Richard Thonig from the IASS explains, the political parties were categorised according to three distinct energy transition strategies or pathways: "In the state-centred approach, the task of planning the energy transition is left to experts, who prescribe how exactly grid expansion or the nuclear and coal phaseout should proceed. In the market-centred strategy, market actors are trusted to determine the specifics of the future energy system and the government's role is limited to defining the boundary conditions of the transition. Grassroots-centred strategies, by contrast, aim for a decentralised, citizen-led energy transition." The study shows how the three approaches manifest in national climate targets, renewable electricity targets, and the flexibility preferences of government and opposition political parties.

Flexibility options are required to deal with the challenge of intermittent renewable electricity. To ensure an uninterrupted electricity supply, electricity generation and consumption need to be balanced. This can be achieved through cross-border electricity trading, the development of storage facilities, or the installation of additional generation capacities, based, for example, on biomass or concentrated solar power.

Strong goals, weak strategy

Across the political spectrum, researchers found a similar level of ambition with regard to decarbonisation and the expansion of renewables among parties and citizens alike. Thus, contrary to their expectations, the different political ideologies had hardly any effect on energy policy preferences. All three pathways foresee more stringent decarbonisation targets over time, ranging from 75% to 100% by 2050 (compared to 1990). While there is no significant ideologically motivated difference in overall ambition, the decarbonisation targets set by the market-centred strategy are somewhat lower (75% to 80% by 2050) than those of the grassroots-centred (85% to 95%) and state-centred (75% to 100%) pathways.

However, to have any chance of meeting these targets, governments now need to make up for lost time. "Regardless of the strategies they pursue - grassroots, state-centred or market-centred - none of the parties has a plan that is even remotely clear about how they intend to ensure a stable and reliable future supply of electricity in the absence of sunshine or wind," summarises co-author Johan Lilliestam. "Climate targets that are compatible with the Paris Agreement call for the decarbonisation of the European electricity system well before the year 2050. To allow for that possibility, governments now urgently need to adopt plausible policy pathways for achieving that goal." For the rapidly emerging renewable electricity system, flexibility is an issue that needs far more political attention.

The outbreak of coronavirus disease (COVID-19) caused by SARS-CoV-2 virus continues to cause human infection and mortality worldwide. Currently, there are no specific viral protein-targeted therapeutics available. Viral nucleocapsid protein is a potential antiviral drug target, serving multiple critical functions during the viral life cycle. However, the structural information of SARS-CoV-2 nucleocapsid protein remains unclear.

In this article, the authors have determined the 2.7 Å crystal structure of the N-terminal RNA binding domain of SARS-CoV-2 nucleocapsid protein. Although the overall structure is similar as other reported coronavirus nucleocapsid protein N-terminal domain, the surface electrostatic potential characteristics between them are distinct. Further comparison with mild virus type HCoV-OC43 equivalent domain demonstrates a unique potential RNA binding pocket alongside the β-sheet core. Complemented by in vitro binding studies, the authors data provides several atomic resolution features of SARS-CoV-2 nucleocapsid protein N-terminal domain, which could guide the design of novel antiviral agents specifically targeting to SARS-CoV-2.

The study by the Department of Political Science at Aarhus BSS shows that the growing trust crisis observed in many Western democracies in recent decades cannot merely be attributed to news criteria from the media and prioritisation of personal-interest stories. Citizens play a significant role in the rapid spread of these types of articles at the expense of positive stories.

"People are better at remembering information about selfish politicians and are better and more motivated to forward that type of information to other people compared to information that focuses on political substance," explains Troels Bøggild, associate professor in political science at Aarhus BSS, Aarhus University.

"This is because there is an inherent bias in human memory that affects the type of political information we pass on in our social network. This means that citizens are part of exaggerating the problem of selfish politicians," he continues.

Troels Bøggild, together with Associate Professor Lene Aarøe and Professor Michael Bang Petersen from the Department of Political Science at Aarhus BSS, Aarhus University, is behind the study titled "Citizens as Complicits: Distrust in Politicians and Biased Social Dissemination of Political Information ", which has just been published in the prestigious journal American Political Science Review.

Gossip lives on

The conclusions of the study are based on a number of internet-based experiments using a representative sample of 3,353 participants in the US. The experiments were carried out in the form of a telephone game. The participants in the first group read an entire news article, which they then recounted to the next group, who then recounted it to another group. Only the information considered important survives such treatment.

"We observed that people pick up and communicate more about strategy and the selfish behaviour of politicians than the political content itself," says Troels Bøggild. He continues:

"We can also see that mistrust spreads. When negative information about politicians is overrepresented, people who receive it second and third hand will also have less trust in those politicians and support their political decisions to a lesser extent. That's the crux of it," says Troels Bøggild.

It was once a survival mechanism

According to Aarhus BSS researchers, this innate psychological tendency stems from the history of human development, where it was an evolutionary advantage to pay particular attention to leaders who lined their own pockets at the expense of the community.

"At that time, there were no formal control bodies to keep leaders in check, so this was people's way of protecting themselves against authoritarian leaders and non-cooperative behaviour," says Troels Bøggild.

The researchers are now applying this to a political context, and linking it to possible negative consequences for political discourse. The behaviour of politicians, the news values of media, and the level of attention of citizens for politicians who abuse their position of power to promote their own interests, are all key ingredients in this dynamic.

However, the researchers stress that the attention people give to personal interest stories is not necessarily an issue. Together with the media, vigilant citizens can prevent corrupt politicians from coming to power.

The coronavirus SARS-CoV-2 is known to infect cells via the receptor ACE2. An international research team under German-Finnish coordination has now identified neuropilin-1 as a factor that can facilitate SARS-CoV-2 entry into the cells' interior. Neuropilin-1 is localized in the respiratory and olfactory epithelia, which could be a strategically important localization to contribute to SARS-CoV-2 infectivity and spreading. Experts from the German Center for Neurodegenerative Diseases (DZNE), Technical University of Munich, University Medical Center Goettingen, University of Helsinki and other research institutions now published their findings in the journal "Science".

The coronavirus SARS-CoV-2 can affect various organs such as the lung and kidneys and also trigger neurological symptoms, including a temporary loss of smell and taste. The spectrum of symptoms of the associated disease - known as COVID-19 - is therefore quite complex. A related virus, SARS-CoV, led to a much smaller outbreak in 2003, possibly because the infection was limited to the lower respiratory system, making the virus less transmissible. SARS-CoV-2, in contrast, additionally infects the upper respiratory system including the nasal mucosa and, in consequence, spreads rapidly through active viral shedding, e.g. when sneezing.

Door opener to the cell

Tissue tropism reflects the ability of a virus to infect specific cell types in different organs. It is determined by the availability of docking sites, so-called receptors, on the surface of cells. These allow docking to and penetration into the cells. "The starting point of our study was the question why SARS-CoV and SARS-CoV-2 that both use ACE2 as a receptor cause different diseases," explained Mikael Simons, a research group leader at the DZNE's Munich site and professor of molecular neurobiology at the Technical University of Munich, whose team was involved in the current studies, together with Giuseppe Balistreri's group at the University of Helsinki.

To understand how these differences in tissue tropisms can be explained, the researchers took a look at the viral "spike proteins" that are essential for virus entry. "The SARS-CoV-2 spike protein differs from its older relative by the insertion of a furin cleavage site," explained Simons. "Similar sequences are found in the spike proteins of many other highly pathogenic human viruses. When we realized that this furin cleavage site is present in the SARS-CoV-2 spike protein, we thought that this might lead us to the answer." When proteins are cleaved by furin, a specific amino acid sequence becomes exposed at its cleaved end. Such furin cleaved substrates have a characteristic pattern that are known to bind to neuropilins at the cell surface.

Experiments using cells cultured in the laboratory, in conjunction with artificial viruses that mimick SARS-CoV-2 as well as naturally occurring virus, indicate that neuropilin-1 is able to promote infection in the presence of ACE2. By specifically blocking neuropilin-1 with antibodies, infection was suppressed. "If you think of ACE2 as a door to enter the cell, then neuropilin-1 could be a factor that directs the virus to the door. ACE2 is expressed at very low levels in most cells. Thus, it is not easy for the virus to find doors to enter. Other factors such as neuropilin-1 might be necessary to help the virus," explained Simons.

A potential way into the nervous system

Since loss of smell is among the COVID-19 symptoms and neuropilin-1 is mainly found in the cell layer of the nasal cavity, the scientists examined tissue samples from deceased patients. "We wanted to find out whether cells equipped with neuropilin-1 are really infected by SARS-CoV-2, and found that this was the case," said Simons. Additional experiments in mice showed that neuropilin-1 enables transport of tiny, virus-sized particles from the nasal mucosa to the central nervous system. These nanoparticles were chemically engineered to bind to neuropilin-1. When the nanoparticles were administered to the nose of the animals, they reached neurons and capillary vessels of the brain within few hours - in contrast to control particles without affinity for neuropilin-1. "We could determine that neuropilin-1, at least under the conditions of our experiments, promotes transport into the brain, but we cannot make any conclusion on whether this is also true for SARS-CoV-2. It is very likely that this pathway is suppressed by the immune system in most patients," explained Simons.

A starting point for future therapies?

"SARS-CoV-2 requires the ACE2 receptor to enter the cells, but other factors such as neuropilin-1 may be required to support its function," said Simons. "However, at present we can only speculate about the molecular processes involved. Presumably, neuropilin-1 catches the virus and directs it to ACE2. Further investigations are needed to clarify this issue. It is currently too early to speculate whether blocking neuropilin could be a viable therapeutic approach. This will have to be addressed in future studies."

In a major breakthrough an international team of scientists, led by the University of Bristol, has potentially identified what makes SARS-CoV-2 highly infectious and able to spread rapidly in human cells. The findings, published in Science today [20 October] describe how the virus's ability to infect human cells can be reduced by inhibitors that block a newly discovered interaction between virus and host, demonstrating a potential anti-viral treatment.

Unlike other coronavirus, which cause common colds and mild respiratory symptoms, SARS-CoV-2, the causative agent of COVID-19, is highly infective and transmissive. Until now, major questions have remained unanswered as to why SARS-CoV-2 readily infects organs outside of the respiratory system, such as the brain and heart.

To infect humans, SARS-CoV-2 must first attach to the surface of human cells that line the respiratory or intestinal tracts. Once attached, the virus invades the cell then replicates multiple copies of itself. The replicated viruses are then released leading to the transmission of SARS-CoV-2.

The virus's process of attachment to and invasion of human cells is performed by a viral protein, called the 'Spike' protein. Understanding the process by which the 'Spike' protein recognises human cells is central to the development of antiviral therapies and vaccines to treat COVID-19.

In this breakthrough study, the research groups in Bristol's Faculty of Life Sciences, Professor Peter Cullen from the School of Biochemistry; Dr Yohei Yamauchi, Associate Professor and virologist from the School of Cellular and Molecular Medicine, and Dr Boris Simonetti, a senior researcher in the Cullen lab, used multiple approaches to discover that SARS-CoV-2 recognises a protein called neuropilin-1 on the surface of human cells to facilitate viral infection.

Yohei, Boris and Pete explained: "In looking at the sequence of the SARS-CoV-2 Spike protein we were struck by the presence of a small sequence of amino acids that appeared to mimic a protein sequence found in human proteins which interact with neuropilin-1. This led us to propose a simple hypothesis: could the Spike protein of SARS-CoV-2 associate with neuropilin-1 to aid viral infection of human cells? Excitingly, in applying a range of structural and biochemical approaches we have been able to establish that the Spike protein of SARS-CoV-2 does indeed bind to neuropilin-1.

"Once we had established that the Spike protein bound to neuropilin-1 we were able to show that the interaction serves to enhance SARS-CoV-2 invasion of human cells grown in cell culture. Importantly, by using monoclonal antibodies - lab-created proteins that resemble naturally occurring antibodies - or a selective drug that blocks the interaction we have been able to reduce SARS-CoV-2's ability to infect human cells. This serves to highlight the potential therapeutic value of our discovery in the fight against COVID-19."

Intriguingly, scientists at the Technical University of Munich, Germany and the University of Helsinki, Finland, have independently found that neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity.

Together the Bristol researchers concluded: "To defeat COVID-19 we will be relying on an effective vaccine and an arsenal of anti-viral therapeutics. Our discovery of the binding of the SARS-CoV-2 Spike to neuropilin-1 and its importance for viral infectivity provides a previously unrecognised avenue for anti-viral therapies to curb the current COVID-19 pandemic."

Helping to explain what makes SARS-CoV-2 so capable of infecting human cells, researchers in two independent studies discovered that the virus's spike protein recognizes and binds a protein on the human cell surface called neuropilin-1. This facilitates its ability to enter and infect cells, they suggest. Demonstrating a potential anti-viral treatment, the findings of both studies also describe how the virus's ability to infect human cells through neuropilin-1 can be reduced by inhibitors. Compared to SARS-CoV, which led to a much smaller outbreak in 2003, SARS-CoV-2 spreads rapidly through active pharyngeal viral shedding. Despite these differences, uptake of both viruses is mediated by the identical cellular receptor, ACE2. One hypothesis to explain the enhanced spreading of SARS-CoV-2 is the presence of a unique cleavage site in the SARS-CoV-2 spike protein, the presence of which could potentially create additional human cell surface receptor binding sites. In looking at the sequence of the SARS-CoV-2 spike protein, James Daly and colleagues identified the presence of a small sequence of amino acids that appeared to mimic a protein sequence found in human proteins that interacts with neuropilin-1. This led them to propose the spike protein of SARS-CoV-2 associates with neuropilin-1 to aid viral infection, a hypothesis they confirmed with a range of structural and biochemical approaches. As well, by knocking out neuropilin-1 in human cells, and, in another test, using a monoclonal antibody against neuropilin-1, they were able to reduce SARS-CoV-2's ability to infect cells in culture. A second study independently found that neuropilin-1 facilitates SARS-CoV-2 cell entry and infectivity. In this work Ludovico Cantuti-Castelvetri et al., seeking to inform the reported disturbance of olfaction in a large fraction of COVID-19 patients, analyzed a series of autopsies from six COVID-19 patients. They detected infection of the olfactory epithelium in five out of six. The infected olfactory epithelial cells showed high expression of neuropilin-1, the authors report. While the focus to date in SARS-CoV-2 entry has been almost entirely on the role of ACE2, Cantuti-Castelvetri et al. note, the expression pattern of ACE2 does not match tissue tropism of SARS-CoV-2. This raises the possibility that co-factors are required to facilitate virus-host cell interactions in cells with low ACE2 expression. "[Neuropilin-1] could represent such an ACE2 potentiating factor," Cantuti-Castelvetri et al. say.

During the first wave of COVID-19, which paralyzed the world in spring, it was initially thought that effective hand washing and 2-metre social distancing would help prevent the highly contagious virus. Scientists, however, have now come to the conclusion that proper indoor ventilation is even more effective. It was also found that SARS-CoV-2 is rather moderately infectious and a person would need to remain in a poorly ventilated room for a considerable amount of time to receive an infectious dose of SARS-CoV-2.

Since the first coronavirus SARS-CoV-1 that broke out in Hong-Kong has been proven to be transmitted across long distances in the air, there is a good reason for the scientists, after hearing the large droplets theory, to raise the question of whether there is a transmission risk of the current SARS-COV-2 virus (causing the coronavirus disease COVID-19) beyond 2 metres.

Head of the TalTech Nearly Zero Energy Buildings Research Group, Professor Jarek Kurnitski says, "Multiple studies provided quickly strong scientific evidence for successful indoor airborne transmission of COVID-19 in inadequately ventilated environments. The virus is transmitted via saliva droplets with a size from 0.5 micrometre up to a few thousand micrometres produced by a person by talking, sneezing, coughing, or even just breathing."

The point is that small and large droplets act completely differently. Tiny droplets below 5 micrometres do not settle on surfaces, they remain airborne and follow airflow streamlines for tens of meters. Large droplets above 100 micrometres in diameter fall down like rocks - they do not travel farther than 1.5 meters even by coughing. The air exhaled by humans contains mainly droplets with diameter in the range of 1-10 micrometres. Until this spring, it was held in the medical literature and guidelines that droplets larger than 5 micrometres fall down at the distance of up to 2 meters (which is why it was concluded that 2-metre social distancing would ensure complete safety). By now, however, scientists have found out that this was a misconception or even a long-persisting erroneous medical dogma. Aerosol physics shows convincingly that in reality only droplets larger than 50 micrometres fall down at a distance of 2 meters, while smaller ones remain suspended in the air and travel farther. Thus, acknowledging this tenfold error fundamentally changed the understanding of the spread of virus particles and it was realized that the largest number of exhaled droplets travel far and the virus can remain infectious in aerosol particles for up to 3 hours.

"By breaking this medical dogma, researchers also gave an important signal regarding the measures applied to prevent the spread of COVID-19 that led to the paralysis. Measures can and must be applied taking into account the known transmission routes, which is why it is important to know that the disease is transmitted by aerosols, i.e. tiny droplets suspended in air. This means that you can get the virus in two ways: in close contact, where the concentration of aerosols and larger droplets in close proximity of the infected person is very high, or farther away in inadequately ventilated rooms, where the concentration of aerosols remains so high that a person can get an infectious dose for example within an hour spent in the same room with an infected person," Professor Kurnitski says.

According to academician Kurnitski, the following engineering controls targeting airborne transmission should be applied as a preventive measure in indoor spaces:

sufficient outdoor air ventilation should be applied as the main control (in principle, it does not matter whether outdoor air enters through a ventilation supply duct or a window, the amount of air is important);

if the building does not have a functioning ventilation system, portable air cleaners with fine particle filters should be used to clean indoor air;

in addition, viral contamination can be deactivated by applying short-wavelength ultraviolet (UV-C) light, which is used for example in certain hospital settings.

Ventilation systems with recirculation air that circulate a part of the extract air from a room into the supply air duct, leaving virus particles recirculating in the ventilation system, pose a particular challenge. It is necessary to increase outdoor air supply in such systems. If a system cannot be switched to fully outdoor air, filtration of extract air must be improved by installing more effective filters.

According to the generally recognised infection control classification, the impact of engineering controls is considered to be greater than that of the second most important, currently however most widely applied administrative measures (closing of institutions, canceling of events, etc.). Wearing personal protective equipment (e.g. face masks) is considered to be the least effective measure in preventing the spread of the virus.

A total of 36 researchers from all over the world published the article on the topic titled "How can airborne transmission of COVID-19 indoors be minimised?". In this research group, Estonian researchers were represented by a civil engineer from TalTech, academician Jarek Kurnitski. Prior to publication of the article, a joint petition on the same topic was signed by 239 scientists and submitted to the World Health Organisation (WHO) with a request to acknowledge that the virus is transmitted by aerosols so that ventilation solutions could be implemented to prevent the spread of the virus. As a result, the WHO and other health authorities acknowledged that COVID-19 is spread not only by large droplets but also by tiny aerosol particles remaining in the air for hours and traveling tens of meters.

Cuscuta spp., also known as dodder, is a parasitic vine which grafts to the host plant using special suckers to obtain water, minerals and carbohydrates. The parasite also attacks and damages crops such as oilseed rape, sweetcorn, soy, flax or clover. Although the infection generally goes undetected by the host, some species of tomato actively defend themselves by forming wooden tissue which prevents the suckers from penetrating the plant. In earlier research, the biologists at FAU discovered that these tomatoes possess a special receptor, the Cuscuta receptor 1 (CuRe1), which triggers the defence mechanism. However, until now it was unclear how the receptor recognises the danger posed by the dodder.

The researchers have now succeeded in answering this question: the dodder possesses a specific marker in its cellular wall, a glycine-rich protein (GRP). Using its receptor CuRe1, the tomato is able to recognise the molecular pattern of the GRP and identify the dodder as a pathogen, and triggers the immune reaction as a result. The new findings concerning the molecular dialogue between the Cuscuta marker and the tomato receptor may help to increase the resistance of crop plants against parasitic plants.