Culture

Has COVID-19 knocked us onto our backsides?

image: Jacob Barkley, Ph.D., professor in Kent State University's College of Education, Health and Human Services, co-authored a study examining COVID-19's effects on physical activity and sedentary behavior in university students and employees.

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Photo Kent State University

Because of the COVID-19 pandemic, most universities across the United States transitioned from face-to-face classes to remote learning, closed campuses and sent students home this past spring. Such changes, coupled with social distancing guidelines, have altered social interactions and limited our access to fitness facilities, parks and gymnasiums. This is concerning as positive social interaction and access to exercise facilities both promote physical activity. Recently, a group of Kent State University researchers sought to examine the impact of these pandemic-related changes upon physical activity and sedentary behavior, specifically sitting, across the university population.

Kent State's College of Education, Health and Human Services professors Jacob Barkley, Ph.D., Andrew Lepp, Ph.D., and Ellen Glickman, Ph.D., along with current and former Kent State doctoral students Greg Farnell, Ph.D., Jake Beiting, Ryan Wiet and Bryan Dowdell, Ph.D., assessed the impact of the COVID-19 pandemic on physical activity and sedentary behavior. More than 400 college students, faculty, staff and administrators reported their typical physical activity and sedentary behavior before the COVID-19 pandemic and after the transition to remote learning and the closure of campus.

In this before-and-after comparison, participants reported nearly eight hours more sitting per week after transitioning from face-to-face classes to remote learning. Changes in physical activity were not so straightforward. Those participants who were not highly active before the pandemic actually increased physical activity after the closure of campus and the transition to remote learning, while participants who were highly active before the pandemic experienced a decrease in overall physical during the pandemic.

"It appears that the participants who were most physically active before the pandemic may have been the most negatively affected," Barkley said. "This makes sense as these active individuals are more likely to utilize the fitness facilities that were closed when the pandemic hit. However, the increases in physical activity in participants who were less active before the pandemic were surprising. Perhaps the elimination of a daily commute left them with more time for physical activity. Or perhaps, they started walking just to get out of the house for a bit. Independent of the changes in physical activity, the sample-wide increase in sitting by over an hour per day is concerning as excess sitting is associated with a variety of negative health outcomes, such as cardiovascular disease, diabetes and even a greater risk of dying earlier."

The authors suggest that while many, like those on university campuses, experienced and may continue to experience challenging, pandemic-related changes to their daily routines, it is important that we all work to maintain positive health behaviors despite these challenges. The Kent State researchers recommend the following:

Try to minimize sitting for extended periods of time, and when possible, add in some exercise at home or outside.

For those who are still working or taking classes remotely, try to incorporate a standing desk into your routine and/or plan breaks where you get up and move away from your computer. During those breaks, try to do some light activity, like taking a walk.

Breaking up your sedentary activity by adding some physical activity will not only benefit your physical health; it can improve cognition, productivity and reduce stress.

"There are likely lots of us that could use some stress relief right now," Barkley said. "Getting up and moving can provide just that."

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Kent State University

IL-21 protein a key part of immune response to central nervous system infections

HERSHEY, Pa. -- Researchers at Penn State College of Medicine now better understand the role of a protein, interleukin-21 (IL-21), in the immune system response to infections in the nervous system. The results of their recent study support further investigation into using IL-21 as a therapeutic agent for persistent central nervous system infections.

CD4 T cells in the immune system produce IL-21, which is critical for the development of CD8 tissue-resident-memory (TRM) cells during persistent viral infections of the central nervous system with polyomavirus.

Dr. Aron Lukacher, professor and chair of the Department of Microbiology and Immunology, said the results, published in Science Immunology, demonstrate that IL-21 is an important factor in the development of effective immune responses to chronic infections in the central nervous system including neurodegenerative HIV-AIDS and progressive multifocal leukoencephalopathy (PML), a fatal brain infection caused by JC polyomavirus. PML starts with symptoms including clumsiness, weakness or difficulty speaking or thinking. As it progresses, patients may develop dementia, have vision problems and become unable to speak.

Lukacher's lab created an animal model of JC polyomavirus in mice, called mouse polyomavirus (MuPyV). Their research focuses on strategies to reduce the harmful effects of MuPyV, with the goal of developing translational approaches to improving outcomes for patients with PML and other immunocompromising conditions.

Prior research demonstrated that IL-21 is a key part of immune responses in the body, but the present study investigated the specific mechanisms and role IL-21 plays in the immune response to infection with MuPyV.

The research team, including medical scientist training program student Heather Ren, studied mice that were unable to produce sufficient CD4 T-cells and had similar defects in gene expression related to the development of CD8 TRM cells. They found that injecting IL-21 into cerebrospinal fluid reduced those deficiencies.

"The use of IL-21 as a therapeutic agent for persistent central nervous system infections needs further investigation," Lukacher, a researcher at Penn State Cancer Institute, said. "Whether it needs to be administered directly into the central nervous system or given peripherally, such as intravenous infusion, will require further testing in our model."

Lukacher said future studies will examine whether giving IL-21 to mice with persistent MuPyV infection, both under immunocompetent and CD4 T-cell-deficient conditions, may bolster protective antiviral CD8 T cell responses and keep the viral infection in check.

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Penn State

Watching your waste

In the United States, where food is relatively easy to come by for most of the population, roughly $165 billion worth of it is wasted every year. That's enough to fill 730 college football stadiums. And of the food that is wasted, the majority of it is at the household level.

"In a consumer-based culture, food can become easily devalued, especially when it's relatively cheap, as it is in the U.S., for the most part. And that ends up being a driver for food waste," said Chris Wharton, assistant dean of innovation and strategic initiatives at Arizona State University's College of Health Solutions.

"But if you can show people how much they're wasting and what that means in terms of dollars and cents or lost opportunities for their kids to eat nutritious fruits and vegetables, then you have put value back in the food, and that could potentially drive down food waste."

Wharton and colleagues recently published a study on the subject in the journal Resources, Conservation and Recycling that employed a values-based intervention in an attempt to reduce household food waste in 53 families in the Phoenix area. The study was funded by a $100,000 grant from Rob and Melani Walton Sustainability Solutions in partnership with the city of Phoenix.

Over the course of five weeks, the families that participated in the study were given instructions to read and view different educational material each week that focused on such topics as proper food storage and how to decipher expiration dates. Along with each week's topic, the educational material also highlighted three values commonly associated with food: cost, health and environmental impact.

"Food waste is as much about the knowledge and the skills needed to reduce it as it is about the values we associate with the food that we buy," Wharton said.

At the end of each week, participants weighed and logged how much food waste they had accumulated using a clear plastic bin to store the waste and a food-grade scale to weigh it.

"That was one of the novelties of the study, because that type of objective measurement hasn't really been employed before," Wharton said. "Food waste -- like so many other things that we throw out every day, like plastic -- it just goes into this magic bucket, the trash can, and it just disappears. But if you can see it, then it starts to tell you something about what it means for that to accumulate, day to day, week to week, month to month, year to year."

In fact, in qualitative data obtained from participants' exit interviews following the study, several families reported that watching their food waste build up in the clear bin acted as a sort of feedback mechanism that prompted them, and even their kids, to want to waste less.

The results of the study showed that the intervention was successful in reducing the families' food waste by an average of 28%. And in a follow-up measurement taken two weeks after the intervention, researchers noted a slight increase in food waste from the families' postintervention percentage, but still an overall significantly lower percentage of food waste than their baseline amount, measured before the intervention.

While those results are statistically significant, the study only scratched the surface of understanding the values we associate with food and how they influence food waste behavior. Going forward, Wharton and his colleagues want to learn more about that in order to develop a predictive model to improve future interventions.

"The approach to revaluate food by trying to attach it to concerns about the environment or health or finances played out interestingly, because different participants found different things more or less important, so it's not totally clear yet what all the drivers of food waste are amongst individuals," he said.

"There's some sense (according to research) that the elderly may waste a little bit less than younger generations or that wealthier families waste a little bit more than less wealthy families. But there's just not any real consensus in the literature on what predisposes people to waste more or less. There are lots of factors that I think could be really important, like culture, emotions and habitation. And if we can figure out what those are, we can develop better interventions."

Wharton encourages any families interested in reducing their own food waste to visit the website where the same educational materials used by study participants are accessible to the general public.

"Certainly any family can do this," he said. "It just takes a little initiative."

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Arizona State University

UQ tech could offer 'faster, cheaper and mobile' COVID-19 diagnosis

image: A simple dipstick allows genetic material to be extracted in as little as 30 seconds.

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The University of Queensland

Technology that helps to quickly extract and analyse genetic material could be used for cheap, accurate and mobile COVID-19 testing, including at airports and remote testing centres.

'Dipstick' technology, developed by the University of Queensland's Professor Jimmy Botella and Dr Michael Mason, allows genetic material to be extracted in as little as 30 seconds, with a full molecular diagnosis in 40 minutes.

"That process is currently achieved using large and expensive commercial set-ups that require multistep procedures and specialised laboratory equipment," Professor Botella said.

"In contrast, our dipstick tech is incredibly cheap and can be used virtually anywhere, without the need for specialised equipment or a laboratory.

"Our tech enables the purification of DNA and RNA nucleic acids from patient samples - a critical step in COVID-19 diagnosis.

"Combined with a portable diagnostic machine we've developed - which fits in your hand and can be powered by a car's cigarette lighter connection - we could enable faster identification and isolation of positive patients, helping to reduce the spread of the disease.

"We're hoping it will be used to expand COVID-19 diagnostic testing to non-laboratory environments such as airports, remote testing centres and GP clinics."

The process can be used to extract genetic material from most living organisms, including people, livestock, bacteria and viruses.

Dr Michael Mason said the team had already applied the technology in other areas, primarily to fight plant pathogens.

"We've successfully used the dipsticks to identify diseases associated with fresh produce and important crops that are critical for feeding some of the world's poorest people," Dr Mason said.

"Even in remote locations, such as isolated plantations in Papua New Guinea, we've successfully used the technology to identify a pathogen killing coconut trees."

"Really, this technology could be used to detect almost any disease, anywhere."

The researchers said their dipsticks can be produced quickly, cheaply and in bulk using a household pasta maker.

"It was quite a surprise, in a year full of surprises," Professor Botella said.

"Using a low-cost pasta maker, wax and filter paper, we are able to rapidly make hundreds of dipsticks, ready to be used, in only a few minutes.

"The simplicity of the manufacturing process and the low-cost and accessibility of the required materials is a significant advantage of this technology.

"It means it can benefit users in modern research laboratories as well as low-resource facilities in developing countries, high schools and small university teaching labs.

"It's faster, cheaper and mobile, so let's put it to work."

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University of Queensland

Invasional meltdown in multi-species plant communities

image: Plant pots with plants used during the experiment.

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Zhijie Zhang

Invasive alien plant species can pose a serious threat to native biodiversity and to human well-being. Identifying the factors that contribute towards invasion success is therefore crucial. Previous studies on biological invasions have focused mainly on interactions between one alien and one native species, attributing invasion success to the superior competitive ability of the invading aliens. Very few experiments have examined them in multi-species plant communities.

A new experiment by ecologists based at the University of Konstanz (Germany), the Northeast Institute of Geography and Agroecology at the Chinese Academy of Sciences, Taizhou University (both in China), the French National Research Institute for Sustainable Development and the Joint Research Unit for Plant-Microorganism-Environment Interactions (France) addresses this research gap by considering competition among plants in communities comprised of several plant species, both alien and native. The results, which appear in the latest issue of Nature Ecology and Evolution, pinpoint one major reason for invasion success and subsequent invasional meltdown to soil microbes, especially fungal endophytes.

Soil microbes a major driver of invasion success

"Plants compete in different ways", explains Zhijie Zhang, first author on the study and a doctoral researcher in the University of Konstanz?s Ecology group led by Professor Mark van Kleunen. "The most intuitive way is competition for resources such as nutrients and sunlight. But competition can also occur through other trophic levels, for instance in relation to herbivores and especially in regard to soil microbes (fungi, bacteria and other small organisms that live below ground). Our study shows that fungal endophytes, which spend at least part of their life cycle inside plants, are key to explaining invasion success".

Previous studies have revealed that plants modify the community of soil microbes as they grow, which affects both their own development and that of plants which later grow on this soil ("soil-legacy effect"). However, exactly how soil-legacy effects impact competitive outcomes between alien and native plants in multi-species communities had remained unclear. To address this issue, the researchers conceived a large multi-species experiment consisting of two stages. First, soil was conditioned with one of six native plant species, with one of four aliens, or, as a control, without any plant. In a second step, on these soils, ten plant species (either native or alien) were grown without competition, with competition from conspecific plants, or with competition from another species, thus mimicking different competition scenarios in nature. To assess the role of microbes, the researchers further analysed how soil-conditioning species affected the soil microbial communities and how the soil microbial communities affected later plants, taking biomass production above ground as an indication of competitive ability.

Invasional meltdown in multi-species plant communities

The study revealed several things: First, there was no evidence of superior competitive ability among the naturalised aliens if the soil they were grown on had not undergone any conditioning. In other words, aliens did not prove to be more competitive than natives in two-species communities, a finding that challenges previous theories on invasion success. Soil conditioned by aliens, however, did affect competitive outcomes between natives and aliens, with aliens producing much more biomass than native plants. "In this scenario, the aliens proved much more competitive than their native rivals, lending further credence to the invasional meltdown hypothesis", explains Zhang.

This hypothesis posits that the establishment of one alien species in a non-native habitat can facilitate the invasion of other alien species in the same environment. The study by Zhang et al. pinpoints the underlying mechanism to the soil microbiome: "Our analyses reveal that the legacy effect of soil-conditioning species on later species became less negative as their microbial communities became less similar", elaborates Zhang. Aliens were observed to share fewer fungal endophytes with other aliens than with native species, which comes with a lower chance of fungal endophytes spilling over. "The idea, which is also referred to as 'novelty', is that two species that share few fungal endophytes affect each other less negatively than two species that share many endophytes", concludes Zhang. "More research needs to be carried out, but we are positive that soil microbes are crucial to invasion success and invasional meltdown in multi-species communities".

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University of Konstanz

Cyanobacteria as "green" catalysts in biotechnology

image: Cyanobacteria are environmentally friendly and readily available biocatalysts for the production of new chemicals and, thanks to researchers at TU Graz, could soon be used in large-scale technological applications.

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Lunghammer - TU Graz

Cyanobacteria, despite staining water green through their special pigments, are colloquially known as "blue-green algae", and convert light energy into chemical energy particularly effectively thanks to their highly active photosynthetic cells. This makes them attractive for biotechnological application, where they could be used as environmentally friendly and readily available biocatalysts for the production of new chemicals using specifically introduced enzymes.

Limited light availability

What sounds good in theory, is still facing obstacles in the practical large-scale technological implementation. A decisive limiting factor is currently the availability of light, as Robert Kourist from the Institute of Molecular Biotechnology at Graz University of Technology explains: "When cyanobacteria are densely grown, i.e. in high concentrations, only the cells located on the outside receive enough light. Inside it's pretty dark. This means that the amount of catalyst cannot be increased at will. After a cell density of a few grams per litre, the photosynthetic activity and thus the productivity of the cells decreases sharply. This is of course a considerable disadvantage for large-scale biotechnological production."

By comparison, previously established biocatalysts such as yeasts can be used with cell densities of 50 grams per litre and more. The established production organisms have the major disadvantage that they depend on agricultural products as a basis for growth and thus consume many resources. "Algae-based catalysts can be grown from water and CO2, so they are 'green' in a two-fold sense. For this reason, intensive efforts are under way to increase the catalytic performance of cyanobacteria," said Kourist.

Making better use of available light

Together with Ruhr University Bochum and the Finnish University of Turku, the algae working group at TU Graz has now succeeded in increasing precisely this catalytic performance by specifically redirecting the photosynthetic electron flow to the desired catalytic function. "For the first time, we were able to measure the supply of photosynthetic energy directly in the cells in a time-resolved manner so that we were able to identify bottlenecks in the metabolism," explains Marc Nowaczyk from the Chair of Plant Biochemistry at the Ruhr University Bochum.

"We have switched off a system in the genome of the cyanobacterium that is supposed to protect the cell from fluctuating light. This system is not necessary under controlled cultivation conditions, but consumes photosynthetic energy. Energy that we prefer to put into the target reaction," explains Hanna Büchsenschütz, doctoral student at TU Graz and first author of the study. In this way, the problem of low productivity of cyanobacteria due to high cell densities can be solved. "To put it another way, we can only use a certain amount of cells. That's why we have to make the cells go faster. We have developed a method using so-called metabolic engineering that makes cyanobacteria a great deal more mature for biotechnological application," said Kourist.

In addition to increasing the productivity of the cell itself through targeted interventions at the gene level, the Graz researchers are also working on new concepts for the algae cultivation process. One approach is to introduce light sources directly into the cell suspension, for example via mini LEDs. New geometries are also being experimented with. Thus, cyanobacteria in the form of encapsulated small spheres, so-called "beads", can absorb more light overall. Robert Kourist comments: "It is very important to develop all measures on the way to large-scale industrial application of algae-based biocatalysts in an integrated way. This is only possible with interdisciplinary research that looks at the function of an enzyme in the same way as we look at engineering in the photosynthetic cell."

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Graz University of Technology

How narcissistic leaders infect their organizations' cultures

Mirror, mirror on the wall, who's the fairest of them all? The answer: not the organizations led by narcissists.

A new paper by Berkeley Haas Prof. Jennifer Chatman and colleagues shows not only the profound impact narcissistic leaders have on their organizations, but also the long-lasting damage they inflict. Like carriers of a virus, narcissistic leaders "infect" the very cultures of their organizations, the researchers found, leading to dramatically lower levels of collaboration and integrity at all levels--even after they are gone.

The paper, "When 'Me' Trumps 'We': Narcissistic Leaders and the Cultures they Create," in-press and published online by The Academy of Management Discoveries. It is co-authored by Charles A. O’Reilly of Stanford’s Graduate School of Business (MBA 71 and PhD 75), and former Berkeley Haas PhD student Bernadette Doerr.

In previous research about toxic leaders, Chatman and her colleagues found that narcissistic CEOs have a dark side that reveals itself slowly over time. Their exploitative, self-absorbed behavior sets them apart from the charismatic, “transformational” leaders they are often confused with. They are also paid more than their non-narcissistic peers, and there’s a larger gap between their pay and those of other top executives in their companies, often because they are so good at unfairly claiming credit for other’s accomplishments. Narcissistic leaders get their companies involved in more lawsuits, as well, Chatman and her colleagues’ research has found.

Narcissistic leaders have personalities that are profoundly grandiose, overconfident, and dishonest, credit-stealing, and blame-throwing, according to Chatman. They are abusive to their subordinates, think they are superior, don’t listen to experts, create conflict, and believe the rules simply don’t apply to them. They can explode in rage at any sign of disagreement or disloyalty. There’s always an “I” in their conception of the team.

In their latest paper, Chatman and her colleagues conducted a series of five experiments on 1,862 test subjects, as well as a field study that included CEOs of major companies, to discern the impact of narcissists’ bad behavior. The results show not only that leaders high on the narcissism scale are less collaborative and ethical, but also that the cultures of the organizations they lead are less collaborative and ethical. Ultimately, the researchers revealed exactly how narcissists institutionalize less collaborative and ethical behaviors and create lasting damage on employee morale and performance.

“Narcissistic leaders affect the core elements of organizations and their impact on society,” says Chatman, the Paul J. Cortese Distinguished Professor of Management. “Companies organize because they can do something together that no individual could accomplish alone. When narcissistic leaders undermine collaboration, they by definition reduce the effectiveness of an organization. Without integrity, an organization risks its very survival.”

How narcissists affect organizations

There’s a colorful saying that the “fish rots from the head down"—employees see leaders acting like jerks, and they become jerks, too.

But it’s not a simple matter of mimicking the boss. “Narcissists don't create narcissists,” Chatman says. “It's not about doing what the leader does. It's about the leader creating a culture that induces people to act less ethically and less collaboratively than they would otherwise, whether they're narcissists or not.”

That’s because a key driver of employee behavior is their organization’s culture, not just their leader, says Chatman, a pioneering researcher in the field. “Organizational culture outlasts any leader,” she says. “Even after a leader is gone, the culture that has been cultivated has a life of its own.”

Narcissists infect the culture through the policies and practices that they directly influence, or—more often—that they fail to institute. They often choose not to put in place strong policies governing ethical behavior, conflicts of interest, and pay equity between men and women, as well as practices that promote teamwork and encourage people to treat others with civility and respect. On the flip side, they also frequently fail to sanction employees when they violate these shared norms. In effect, people get rewarded for less ethical, less collaborative behaviors, Chatman says.

Actions such as these create lasting organizational damage. When people aren’t able to collaborate, collective accomplishments become harder to attain. Employees’ ability to learn, grow, and gain new expertise withers. When they see leaders take credit for every success and blame others for every failure, employees’ morale sinks and their self-confidence wilts.

While there’s strong evidence that people who are overconfident and unethical generate lower financial performance and undergo more regulatory investigations of ethical breaches than those who are not, Chatman says the jury is still out about whether narcissistic leaders have a strong impact on long-term company performance. That's because many external and competitive variables can affect stock prices, revenues, and profitability. Even so, Chatman argues, narcissists’ penchant for becoming embroiled in lawsuits and ethical breaches, being insensitive to risk because of their overconfidence, and creating low employee motivation is a recipe for poor organizational performance.

Yet the mythology persists: Don’t bold, visionary leaders like Elon Musk of Tesla or Steve Jobs of Apple need to be a little bit narcissistic in order to have the self-confidence to launch innovative and supremely risky ventures? The answer is a definite no, says Chatman. “You can have confidence and be innovative, and not be self-involved, exploitative of others, overconfident, and risk-insensitive,” she says. “Bill Gates is a perfect countervailing example. But somehow, the lay public, especially in the U.S., has developed a view that leaders are supposed to be loud-talking and overconfident.”

How to head off narcissistic leadership

To avoid narcissistic leaders, one obvious solution is to simply not hire them, or allow them to move up. Organizations should put special measures in place to screen for these personality types, Chatman says. A common approach involves asking tough questions to uncover negative behaviors from a wide range of references, not just those a leader provides. However, narcissists are often savvy enough to recognize who is going to sing their praises and who isn't, and will provide a selective list of references. In some cases, executive search firms are enlisted to go beyond references and try to uncover information that is harder to find.

Still, wily narcissists can sometimes evade detection until they’ve been in place for a while. Using 360-degree evaluations from a wide range of employees can help surface self-absorbed leaders, Chatman notes.

Once it becomes clear that a company has a toxic leader at the top, it takes unflagging effort from the board to rein in a narcissist’s worst tendencies, Chatman says. Unfortunately, many boards of directors don’t go far enough in that direction, which is part of the reason why companies have ended up with so many CEOs who are high on the narcissism scale.

Chatman says that one of the best ways to mitigate the damage narcissistic leaders can cause is to base a significant part of their compensation and performance evaluation on the development of their people. Boards can also align a leader’s compensation to the performance of their team, and boards can devise ways to reward collaboration with peers. Measures such as these help ensure leaders cannot circumvent sharing credit and working with others.

Chatman’s findings show that after a narcissist leader gets a strong foothold, removing them is only the first step in repairing the organization. “Boards can't assume that simply by removing a leader, they will be able to change how people in the organization behave,” she says. “The culture leaders helped create will still be embedded in the policies and practices that reward people for prioritizing uncollaborative and unethical behaviors. Turning around this kind of culture will take explicit effort and likely a significant amount of time.”

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University of California - Berkeley Haas School of Business

A small switch with a big impact

T cells play a key role in the human immune system. They are capable of distinguishing diseased or foreign tissue from the body's own, healthy tissue with great accuracy; they are capable of triggering the actions necessary to fight off the troublemakers. The details of this immune response are manifold and the individual steps are not yet fully understood.

Scientists of the universities of Würzburg and Mainz have now figured out new details of these processes, showing that tiny point mutations in a gene can modify T cells to be less aggressive. This could be an advantage after stem cell transplantation which includes T-cell transfusion in order to keep a number of severe side effects in check. The researchers have now published the results of their study in the Journal of Experimental Medicine. The study is led by Dr Friederike Berberich-Siebelt, head of the "Molecular and cellular immunology" research group at the Institute of Pathology of the University of Würzburg.

A protein family with multiple tasks

When T cells detect foreign or altered tissue, such as an infected or tumour tissue, this usually happens through the receptors on their cell surface. These T-cell receptors then send signals into the cell interior, initiating a response. In a first step, they activate a special family of transcription factors - scientifically called NFAT for nuclear factor of activated T-cells. The NFATs then bind to the DNA in the cell nucleus and trigger also the production of cytokines such as interleukin-2.

NFAT is composed of many family members which may have overlapping tasks or assume completely different functions. But that's not all: Like many other proteins in the cell, they can still be modified after their synthesis to customize their function. The recently published study focuses on one specific modification of the NFATc1 "family member" which is called sumoylation.

Advantageous point mutations

"Sumoylation plays a role in different cellular processes such as nuclear transport, programmed cell death or as an antiviral mechanism," Friederike Berberich-Siebelt explains. Sumoylation defects have also been observed in various diseases such as cancer and herpesvirus infections.

In the study now published, the scientists worked with laboratory animals that had two actually insignificant point mutations in the NFATc1 gene which, however, prevent sumoylation. This is not necessarily a disadvantage: "The offspring of these animals is perfectly healthy. The modified NFATc1 even mediates specific signals that reduce the clinical symptoms of multiple sclerosis at least in the animal model," Berberich-Siebelt explains. When using T cells that carry these mutations in stem cell transplantation, they are much less aggressive against the tissues of the host animals than "normal" cells.

Fascinating fundamental research

This effect is due to an increase in interleukin-2 at the beginning of the immune response at the biomolecular level. Interleukin-2 counteracts the differentiation into inflammatory T-cell subtypes and at the same time supports so-called regulatory T cells according to the authors of the study. It is quite possible that this discovery will have consequences for future stem cell transplantation which includes T-cell infusion. When using T cells in which NFATc1 is not sumoylated, this might prevent severe side effects, making the point mutation "a small modification with a big impact" according to Berberich-Siebelt.

To investigate this in more detail, Berberich-Siebelt and her team will continue to research the possibilities of therapeutic implementation within the framework of the Collaborative Research Center/Transregio "Control of graft-versus-host and graft-versus-leukaemia immune responses after allogeneic stem cell transplantation" funded by the German Research Foundation (DFG). "We want to find out whether CRISPR/Cas9 gene editing can be applied to human T cells to exhibit just the right amount of activity during hematopoietic stem cell transplantation," the scientist says.

But the new findings are also relevant independently of these potential consequences for therapeutic applications. "We are basically interested in understanding the fine regulation in cells, such as the T-cell receptor signalling and the function of NFAT family members and their isoforms in this context," says Berberich-Siebelt who finds the newly published results "fascinating". After all, the scientists did not have to switch off a gene or activate it excessively as is often the case in research. Instead, two actually harmless point mutations and subtle direct effects were sufficient to ultimately flip the switch from inflammation, autoimmunity and rejection to tolerance. A small shift of the focus at the beginning of the immune response had been sufficient to accomplish this.

Credit: 
University of Würzburg

Reducing the high social cost of death

image: An unexpected loss of a loved one can lead to a range of ramifications if not dealt with properly

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Kyoto University

Japan - How will you cope with the death of your mother or spouse? Their death may disturb your concentration, causing accidents or lowering your productivity. Some bereaved cannot sleep, and others cannot get out of bed. Some lose all appetite, while others binge eat constantly. Some grow alcoholic, and some suicidal. Our responses may depend on our family, culture, community, or belief-systems, but we all struggle to accept our loved ones' deaths.

The cost of grief is not confined to personal mental anguish. It reduces productivity, causes dependency on medicine and social services, and increases mortality risks for survivors. While this is well documented in Europe, we have little data for Japan, the world's most elderly country. To fill this gap, a research team led by Kyoto University is conducting a nationwide survey of bereavement.

"Japan's society is rapidly aging. By 2030, nearly everyone in Japan will suffer the death of a parent, elder relative, spouse, or close friend," explains lead author Carl Becker of the Center for the Promotion of Interdisciplinary Education and Research, who garnered the 2020 Educator Award from the international Association for Death Education and Counseling.

"Recent UK studies suggest that about 10% of bereaved individuals show significant decline in health, resulting in prolonged use of resources. If Japan faces the same percent, the impact will be catastrophic." The team decided to conduct similar surveys throughout Japan with additional questions focusing on economic and lifestyle changes.

Their pilot report -- published in the journal OMEGA -- shows that deeper grief correlates with an overarching decline in quality of life, seen in physical ailments, more down time, and higher rates of medical reliance. Interestingly, lower income families lost more productivity and pharmaceutical expenses, while lower satisfaction with funerals was linked to higher medical costs.

Results show that bereaved Japanese are similar to Europeans in their losses of everything from time, productivity, health, and medical expenses. Factors like the circumstances of death, the loss of income, lack of family or social support, and satisfaction with funeral proceedings can help predict who may need the most help in the future.

"By identifying key problems, we can begin to see what solutions are required to mitigate severe bereavement," states Tohoku University's Yozo Taniyama, second author of the study. "For example, better testing, medical care, and psychological treatment can help people handle unexpected death. More robust financial and social aid can help with the loss of income."

Tradition and rituals appear to facilitate better responses as well. Funeral services offer friends and relations a chance to reconnect and support the bereaved, reducing their loneliness and isolation. Moreover, rituals help the bereaved to come to terms with death.

The research team predicted that people with low or declining incomes would find funeral costs more burdensome. Although that group did lose more time and spend more on pharmaceuticals, they displayed little dissatisfaction with funeral costs. In fact, the people who expressed greater dissatisfaction were those who abbreviated funerals, who later tended to show higher rates of physical as well as psychological problems.

Becker concludes, "Japan has a tradition of ceremonies that bring people together to help the bereaved process their trauma. Much of the world is learning from Japan's traditions that value spiritual bonds with departed loved ones. It is healthier to revere our dead than to try to forget them."

Credit: 
Kyoto University

Statistical model improves analysis of skin conductance

image: With electrodes strapped to two fingers, researchers can read out a signal of electrodermal activity.

Image: 
Sandya Subramanian/MIT Picower Institute

Electrodermal activity - the sweat-induced fluctuations of skin conductance made famous in TV dramatizations of lie-detector tests - can be a truly strong indicator of subconscious, or "sympathetic," nervous system activity for all kinds of purposes, but only if it is analyzed optimally. In a new study in the Proceedings of the National Academy of Sciences, an MIT-based team of scientists provides a new, fast and accurate statistical model for analyzing EDA.

"Only so much of EDA is intuitive just by looking at the signal," said Sandya Subramanian, a graduate student in the Harvard-MIT Health Sciences and Technology program and the study's lead author. Meanwhile, existing mathematical methods of analysis either compute averages of the signal that obscure its instantaneous nature, or inefficiently force measurements into a fit with signal processing models that have nothing to do with what's going on in the body.

To make EDA analysis faster and more accurate for interpreting internal cognitive states (like anxiety) or physiological states (like sleep), the team instead sought a statistical model that matches with the actual physiology of sweat. When stimulated by the sympathetic nervous system, glands under the skin build up a reservoir of sweat and then release it when they are full. This kind of process, called "integrate-and-fire," is also characteristic of diverse natural phenomena like the electrical spiking of nerve cells and geyser eruptions, said senior author Emery N. Brown, Edward Hood Taplin Professor at The Picower Institute for Learning and Memory and the Institute for Medical Engineering & Science at MIT.

A key insight of the study was the recognition that there is a well-established statistical formula for describing integrate-and-fire systems called an "inverse Gaussian" that could provide a principled way to model EDA signals.

"There is a push away from modeling actual physiology to just using off-the-shelf machine learning," said Brown, who is also an anesthesiologist at Massachusetts General Hospital and a Professor at Harvard. "But we would have missed a very simple, straightforward and even elegant description that is a readout of the body's autonomic state."

Led by Subramanian, the study team, which also included MGH researcher Riccardo Barbieri, formulated an inverse Gaussian model of EDA, and then, put it to the test with 11 volunteers who wore skin conductance monitors for an hour as they sat quietly, read or watched videos. Even while "at rest" people's thoughts and feelings wander, creating ample variation in the EDA signal. Nevertheless, after analysis of all 11, the inverse Gaussian produced a tight fit with their actual readings.

The modeling was able to account for smaller peaks in EDA activity than other methods typically exclude and also the degree of "bumpiness" of the signal, as indicated by the length of the intervals between the pulses, Subramanian said.
In 9 of the 11 cases, adding one of a few related statistical models tightened the inverse Gaussian's fit a little further.

Subramanian said that in practical use, an EDA monitoring system based on an inverse Gaussian model alone could immediately be useful, but it could also be quickly fine-tuned by initial readings from a subject to apply the best combination of models to fit the raw data.

Even with a bit of blending of models, the new approach will be quicker, more computationally efficient and readily interpretable than less principled analysis methods, the authors said, because the tight coupling to physiology requires varying only a few parameters to maintain a good fit with the readings. That's important because if the job of an EDA monitoring system is to detect significant deviations in the signal from normal levels, such as when someone feels acute discomfort, that comparison can only be made based on an accurate, real-time model of what a subject's normal and significantly abnormal levels are.

Indeed among the next steps in the work are tests of the model in subjects under a wider range of conditions ranging from sleep, to emotional or physical stimulation, and even disease states such as depression.

"Our findings provide a principled, physiologically based approach for extending EDA analyses to these more complex and important applications," the authors concluded.

Credit: 
Picower Institute at MIT

The best of both worlds: A new take on metal-plastic hybrid 3D printing

image: An approach that extends the use of 3D printers to 3D electronics for future robotics and Internet-of-Things applications

Image: 
Waseda University

Three-dimensional (3D) printing technology has evolved tremendously over the last decade to the point where it is now viable for mass production in industrial settings. Also known as "additive manufacturing," 3D printing allows one to create arbitrarily complex 3D objects directly from their raw materials. In fused filament fabrication, the most popular 3D printing process, a plastic or metal is melted and extruded through a small nozzle by a printer head and then immediately solidifies and fuses with the rest of the piece. However, because the melting points of plastics and metals are very different, this technology has been limited to creating objects of either metal or plastic only--until now.

In a recent study published in Additive Manufacturing, scientists from Waseda University, Japan, developed a new hybrid technique that can produce 3D objects made of both metal and plastic. Professor Shinjiro Umezu, who led the study, explains their motivation: "Even though 3D printers let us create 3D structures from metal and plastic, most of the objects we see around us are a combination of both, including electronic devices. Thus, we thought we'd be able to expand the applications of conventional 3D printers if we managed to use them to create 3D objects made of both metal and plastic."

Their method is actually a major improvement over the conventional metallization process used to coat 3D plastic structures with metal. In the conventional approach, the plastic object is 3D-printed and then submerged in a solution containing palladium (Pd), which adheres to the object's surface. Afterwards, the piece is submerged in an electroless plating bath that, using the deposited Pd as a catalyst, causes dissolved metal ions to stick to the object. While technically sound, the conventional approach produces a metallic coating that is non-uniform and adheres poorly to the plastic structure.

In contrast, in the new hybrid method, a printer with a dual nozzle is used; one nozzle extrudes standard melted plastic (acrylonitrile butadiene styrene, or ABS) whereas the other extrudes ABS loaded with PdCl2. By selectively printing layers using one nozzle or the other, specific areas of the 3D object are loaded with Pd. Then, through electroless plating, one finally obtains a plastic structure with a metallic coating over selected areas only.

The scientists found the adhesion of the metal coating to be much higher when using their approach. What's more, because Pd is loaded in the raw material, their technique does not require any type of roughening or etching of the ABS structure to promote the deposition of the catalyst, unlike the conventional method. This is especially important when considering that these extra steps cause damage not only to the 3D object itself, but to the environment as well, owing to the use of toxic chemicals like chromic acid. Lastly, their approach is entirely compatible with existing fused filament fabrication 3D printers.

Umezu believes that metal-plastic hybrid 3D printing could become very relevant in the near future considering its potential use in 3D electronics, which is the focus of upcoming Internet-of-Things and artificial intelligence applications. In this regard, he adds: "Our hybrid 3D printing method has opened up the possibility of fabricating 3D electronics so that devices and robots used in healthcare and nursing care could become significantly better than what we have today."

This study hopefully paves the way for hybrid 3D printing technology that will enable us to get the best of both worlds--metal and plastic combined.

Credit: 
Waseda University

Mapping the chaos of movement

video: C. elegans are just a curve, which is relatively easy to describe mathematically.

Image: 
Dr. Tosif Ahamed / OIST

The behavior of living organisms might obey the same mathematical laws as physical phenomena, such as weather and the motion of planets, says new research from the Biological Physics Theory Unit at the Okinawa Institute of Science and Technology Graduate University (OIST).

Physics has a history of successfully predicting and modeling motion across vastly different scales, from molecules to colliding black holes. But when it comes to the behavior of living organisms, the concept is still very new. Recent OIST PhD graduate, Dr. Tosif Ahamed, is therefore part of a group of scientists that are pioneers in this field. His research, published in Nature Physics, used a species of a tiny worm, Caenorhabditis elegans, to propose a framework for capturing the mathematical structure underlying moving animals.

"Neuroscience tends to focus on what goes on inside the brain," Dr. Ahamed said. "But this is often expressed through an animal's movement and behavior. Therefore, understanding their behavior gives us a window into their brains. Recently, there has been an explosion of technology that can record the behavior of animals in high resolution."

Professor Greg Stephens, who leads the OIST Unit, added to this, "Remarkable technological progress has enabled new, precision measurements of living systems on all scales, from molecules of DNA to brain cells, to entire organisms. But we currently lack a fundamental framework for understanding the dynamics of these systems and the sequences of measurements over time. Our work reported here will help change that."

C. elegans have been an important species for many groundbreaking projects in biology and neuroscience but it's their simplicity that made them ideal for this study. As Dr. Ahamed explained, mathematically speaking, the shape of worms on a 2D plate is simply a curve, which is relatively easy to describe.

The research team, which included Dr. Antonio Costa from Vrije Universiteit Amsterdam, used high-video recordings of the worm, and converted the shape in each frame to a set of numbers. To do this, they divided the worm into 100 points and measured the tangent angles at these points. The researchers had previously found that a worm's posture could be represented by just four stereotyped shapes, for which they dubbed 'eigenworms'. Essentially, by mixing these eigenworms in different amounts, anyone can draw what a worm looks like at a given instant.

But in this study the researchers looked deeper. Instead of drawing the worm at a single instant, they sought to 'draw' the dynamics of its behavior, essentially to find the structure in a sequence of worm shapes.

The pendulum analogy

Show someone the instantaneous point of a swinging pendulum and they'll be able to imagine what it looks like at that moment in time, but this tells them nothing about what the pendulum is doing. But show someone the current point and an additional point at a previous time, and they'll know everything about both what the pendulum is doing now and what it will do in the future.

The research group took a similar approach when studying the animals, but this was much trickier than with the pendulum. At first the researchers had to develop a new metric of predictability. This measures the duration for which a system's future could be predicted better than just random guessing. They then collected shape sequences and used them to define a worm's current state. The researchers found seven stereotyped shape sequences, all of which were remarkably interpretable.

However, unlike with the pendulum, the researchers couldn't predict the worm's behavior indefinitely. "It's like with the weather," Dr. Ahamed said. "We're at a point where we can predict the weather with a high level of certainty for today and tomorrow but after that it becomes quite random. If I know what a worm is doing now, then I can tell you quite confidently what it's going to do in the next instant. But once we get to two or three seconds later, it becomes more difficult."

Dr. Ahamed wanted to explore why movement so unpredictable. Further analysis of their data hinted that chaotic dynamics might play a role.

Chaotic dynamics refers to systems in which small uncertainties in measurements can make long-term predictions impossible. This can happen even when a system isn't influenced by random fluctuations.

A classic example of this is a double pendulum. Even if multiple double pendulums are started from roughly the same position, the pendulums will make very different motions after a short period of time.

The research group explored these ideas with the worms. They found that if two worms start with similar behaviors, they will continue to act similarly for a short time (around one second) before their behavior diverges. Remarkably, the time it takes for this divergence to occur is determined by a mathematical quantity, which is a fundamental measure of predictability in chaotic systems.

They also looked at the motion through a more geometry-based lens, by mapping all the points that a worm had been to form a shape. Surprisingly, their results showed that the mathematical structure underlying worm behavior is closely related to one which governs energy-conserving phenomena. This was unexpected as worms, like all biological systems, lose energy through environmental friction and muscle use.

"We never expected to find this structure underlying the behavior" explained Dr. Ahamed. "It was definitely the most surprising part of this research."

Although this study looked specifically at C. elegans, the framework developed should be usable across the biological world.

"People generally don't think that living organisms can be mathematically modeled," said Dr. Ahamed. "But there's a finite number of movements that any animal can make and there's a measurable probability that they'll make certain movements over others. We're now at the stage where we can find mathematical frameworks. Next, we'll develop equations and models to explain these frameworks."

Credit: 
Okinawa Institute of Science and Technology (OIST) Graduate University

First rehoming of laboratory dogs in Finland successful but required a great deal of work

image: Researchers at the Faculty of Veterinary Medicine of the University of Helsinki monitored the success of rehoming 16 laboratory beagles in 2015-2018.

Image: 
Andreas Arbelaez/Unsplash

The rehoming of laboratory dogs was the first of its kind in Finland. The rehoming process was started with months of practising basic pet dog skills with the dogs and by familiarising them with the world outside the laboratory.

The practice period lasted from four to six months, depending on the dog.

"However, we found out that the socialisation time was not quite sufficient for all dogs; owners reported that some dogs continued to be timid and suffer from separation anxiety. The laboratory dog rehoming process would be smoother if in the future laboratory dog facilities separated out the defaecation and rest areas, gave dogs access to an outside area and walked them outside on a leash," says Docent Marianna Norring from the Faculty of Veterinary Medicine at the University of Helsinki.

The dogs had been living in packs of eight dogs for two to eight years in the University's laboratory animal facilities, from where they had daily access to an enclosed outside space. They spent the nights in smaller groups of dogs.

At the University, the dogs had participated in both animal cognition and veterinary medical studies. The cognition research provided basic information on canine minds, and a new tranquillising agent suitable for dogs was developed in the veterinary medical study. The University of Helsinki does not currently have laboratory dogs.

The rehoming of laboratory dogs was implemented as a collaboration between SEY Animal Welfare Finland and the University of Helsinki. A large group of individuals participated in socialising the dogs and acquainting them with life outside the facility: animal caretakers, researchers, animal-rights campaigners and dog trainers. The aim was to take into account the individual characteristics of each dog when searching for a new home for them. Whenever possible, dogs were rehomed in pairs. Generally speaking, the new owners have been extremely happy about their new pets.

Credit: 
University of Helsinki

Hunger encourages risk-taking

image: The risk of being caught by a predator is one of the risks that wild animals face when searching for food. Here a shoal of fish meets a blacktip reef shark.

Image: 
Photo: Oliver Krüger

The lives of animals in the wild are full of risky situations with uncertain outcomes. Whether they are exploring new habitats in unfamiliar terrain or searching for new food sources, they run the risk of being caught and killed by a predator. In many instances, their very survival depends on a single decision. Whether an animal decides to take a risk or prefers to avoid danger varies greatly from one individual to another.

"Just as there are humans who are more cautious and others who take more risks, among animals of a particular species there are also individuals that are more or less risk-averse," says population ecologist Prof. Holger Schielzeth of the University of Jena. These differences are to some degree innate, but to a considerable extent they also depend on an individual's development. As Prof. Schielzeth, his Bielefeld colleague Prof. Klaus Reinhold and their research teams have now shown in an extensive meta-analysis, an animal's risk appetite is decisively influenced by the nutritional conditions it experiences while growing up. The researchers report on their findings in the latest issue of the specialist journal Biological Reviews.

Study results involving over 100 animal species compared

The researchers, working with lead author Nicholas Moran, analysed more than 120 experimental studies involving over 100 animal species and the results. Species studied included spiders, insects, crustaceans, fish, amphibians and birds. Common to all the studies was the fact that the animals had experienced phases of good and bad nutrition, and that their risk appetite was measured later in life. There were two opposing hypotheses: "On the one hand, one could assume that animals that have always enjoyed good circumstances and are therefore in a better condition would have more to lose and would therefore be more risk-averse," says evolutionary biologist Reinhold. On the other hand, he adds, a better nutritional status could mean that an animal would escape more easily from a risky situation, and would therefore be more likely to take a risk.

The analysis of the results of all the studies has now made things clear. An insufficient food supply causes animals to engage in higher-risk behaviour: the willingness to take risks rises by an average of 26 per cent in animals that have experienced hunger earlier in their lives.

"We were surprised that this result was so clear and unambiguous," says Schielzeth. The correlation applied to virtually all the behavioural contexts studied, such as exploration behaviour, migration and risky searches for food. There were of course variations in the strength of the effect. Nevertheless, Schielzeth assumes that this correlation could also exist in humans, at least to some extent, as we are, after all, also an "animal species".

This meta-analysis was carried out within the framework of the Collaborative Research Centre Transregio 212, "A Novel Synthesis of Individualisation across Behaviour, Ecology and Evolution: Niche Choice, Niche Conformance, Niche Construction" (NC3), which is based at the universities of Bielefeld and Münster, and in which the University of Jena is also involved. Dr Nicholas Moran is currently an MSCA Research Fellow at the National Institute of Aquatic Resources, Technical University of Denmark.

Credit: 
Friedrich-Schiller-Universitaet Jena

Caring for others is a key driver in getting people to use chatbots for mental health

A new study from North Carolina State University and Syracuse University assessed what would motivate people to use chatbots for mental health services in the wake of a mass shooting. The researchers found that users' desire to help others with mental health problems was a more powerful driver than seeking help for their own problems.

"We saw a sharp increase in mass shootings in the U.S. in recent years, and that can cause increases in the need for mental health services," says Yang Cheng, first author of the study and an assistant professor of communication at NC State. "And automated online chatbots are an increasingly common tool for providing mental health services - such as providing information or an online version of talk therapy. But there has been little work done on the use of chatbots to provide mental health services in the wake of a mass shooting. We wanted to begin exploring this area, and started with an assessment of what variables would encourage people to use chatbots under those circumstances."

The researchers conducted a survey of 1,114 U.S. adults who had used chatbots to seek mental health services at some point prior to the study. Study participants were given a scenario in which there had been a mass shooting, and were then asked a series of questions pertaining to the use of chatbots to seek mental health services in the wake of the shooting. The survey was nationally representative and the researchers controlled for whether study participants had personal experiences with mass shootings.

The researchers found a number of variables that were important in driving people to chatbots to address their own mental health needs. For example, people liked the fact that chatbots were fast and easy to access, and they thought chatbots would be good sources of information. The study also found that people felt it was important for chatbots to be humanlike, because they would want the chatbots to provide emotional support.

But researchers were surprised to learn that a bigger reason for people to use chatbots was to help other people who were struggling with mental health issues.

"We found that the motivation of helping others was twice as powerful as the motivation of helping yourself," Cheng says.

Helping others, in this context, would include talking to a chatbot in order to help a loved one experiencing mental illness from getting worse; finding ways to encourage the loved one to access the chatbot services; or to demonstrate to the loved one that the services are easy to use.

"Our study offers detailed insights into what is driving people to access mental health information on chatbot platforms after a disaster, as well as how they are using that information," Cheng says. "Among other applications, these findings should be valuable for the programmers and mental healthcare providers who are responsible for developing and deploying these chatbots."

Credit: 
North Carolina State University