Culture

New Haven, Conn. -- Alzheimer's disease is known for its slow attack on neurons crucial to memory and cognition. But why are these particular neurons in aging brains so susceptible to the disease's ravages, while others remain resilient?

A new study led by researchers at the Yale School of Medicine has found that susceptible neurons in the prefrontal cortex develop a "leak" in calcium storage with advancing age, they report April 8 in the journal Alzheimer's & Dementia, The Journal of the Alzheimer's Association. This disruption of calcium storage in turns leads to accumulation of phosphorylated, or modified, tau proteins which cause the neurofibrillary tangles in the brain that are a hallmark of Alzheimer's.

These changes occur slowly, building over many years, and can be seen within neurons in the brains of very old monkeys, the researchers report.

"Altered calcium signaling with advancing age is linked to early-stage tau pathology in the neurons that subserve higher cognition," said corresponding author Amy Arnsten, the Albert E. Kent Professor of Neuroscience and professor of psychology and member of the Kavli Institute of Neuroscience at Yale University.

These vulnerable neurons face another problem. As they age, they tend to lose a key regulator of calcium signaling, a protein called calbindin, which protects neurons from calcium overload, and is abundant in the neurons of younger individuals.

"With age, these neurons face a double whammy, with an excessive calcium leak that initiates toxic actions, as well as diminished levels of the protectant, calbindin," said Arnsten.

Neurons in the prefrontal cortex require relatively high levels of calcium to perform their cognitive operations, but the calcium must be tightly regulated. However, as regulation is lost with increasing age, neurons become susceptible to tau pathology and degeneration. Essentially, neurons "eat" themselves from within.

"Understanding these early pathological changes may provide strategies to slow or prevent disease progression," Arnsten said.

WEST LAFAYETTE, Ind. - New insights into the immune response to SARS-CoV-2 infections could bring better treatments for COVID-19 cases.

An international team of researchers unexpectedly found that a biochemical pathway, known as the immune complement system, is triggered in lung cells by the virus, which might explain why the disease is so difficult to treat. The research is published this week in the journal Science Immunology.

The researchers propose that the pairing of antiviral drugs with drugs that inhibit this process may be more effective. Using an in vitro model using human lung cells, they found that the antiviral drug Remdesivir, in combination with the drug Ruxolitinib, inhibited this complement response.

This is despite recent evidence that trials of using Ruxolitinib alone to treat COVID-19 have not been promising.

To identify possible drug targets, Majid Kazemian, assistant professor in the departments of computer science and biochemistry at Purdue University, said the research team examined more than 1,600 previously FDA-approved drugs with known targets.

"We looked at the genes that are up-regulated by COVID-19 but down-regulated by specific drugs, and Ruxolitinib was the top drug with that property," he said.

Within the last few years, scientists have discovered that the immune complement system - a complex system of small proteins produced by the liver that aids, or complements, the body's antibodies in the fight against blood-borne pathogens - can work inside cells and not just in the bloodstream.

Surprisingly, the study found that this response is triggered in cells of the small structures in the lungs known as alveoli, Kazemian said.

"We observed that SARS-CoV2 infection of these lung cells causes expression of an activated complement system in an unprecedented way," Kazemian said. "This was completely unexpected to us because we were not thinking about activation of this system inside the cells, or at least not lung cells. We typically think of the complement source as the liver."

Claudia Kemper, senior investigator and chief of the Complement and Inflammation Research Section of the National Institutes of Health, was among the first to characterize novel roles of the complement system in the immune system. She agreed these latest findings are surprising.

"The complement system is traditionally considered a liver-derived and blood-circulating sentinel system that protects the host against infections by bacteria, fungi and viruses," she said. "It is unexpected that in the setting of a SARS-CoV2 infection, this system rather turns against the host and contributes to the detrimental tissue inflammation observed in severe COVID-19. We need to think about modulation of this intracellular, local, complement when combating COVID-19."

Dr. Ben Afzali, an Earl Stadtman Investigator of the National Institute of Health's National Institute of Diabetes and Digestive and Kidney Diseases, said there are now indications that this has implications for difficulties in treating COVID-19.

"These findings provide important evidence showing not only that complement-related genes are amongst the most significant pathways induced by SARS-CoV2 in infected cells, but also that activation of complement occurs inside of lung epithelial cells, i.e., locally where infection is present," he said.

"This may explain why targeting the complement system outside of cells and in the circulation has, in general, been disappointing in COVID-19. We should probably consider using inhibitors of complement gene transcription or complement protein activation that are cell permeable and act intracellularly instead."

Afzali cautions that appropriate clinical trials should be conducted to establish whether a combination treatment provides a survival benefit.

"The second finding that I think is important is that the data suggest potential benefit for patients with severe COVID-19 from combinatorial use of an antiviral agent together with an agent that broadly targets complement production or activation within infected cells," he said. "These data are promising, but it is important to acknowledge that we carried out the drug treatment experiments in cell lines infected with SARS-CoV2. So, in and of themselves they should not be used to direct treatment of patients."

Kemper added that the unexpected findings bring more questions.

"A currently unexplored and possibly therapeutically interesting aspect of our observations is also whether the virus utilizes local complement generation and activation to its benefit, for example, for the processes underlying cell infection and replication," she said.

About Purdue University

Purdue University is a top public research institution developing practical solutions to today's toughest challenges. Ranked the No. 5 Most Innovative University in the United States by U.S. News & World Report, Purdue delivers world-changing research and out-of-this-world discovery. Committed to hands-on and online, real-world learning, Purdue offers a transformative education to all. Committed to affordability and accessibility, Purdue has frozen tuition and most fees at 2012-13 levels, enabling more students than ever to graduate debt-free. See how Purdue never stops in the persistent pursuit of the next giant leap at https://purdue.edu/.

Journal

Science Immunology

DOI

10.1126/sciimmunol.abg0833

When most Americans imagine an archaeologist, they picture someone who looks like Indiana Jones. Or, perhaps, Lara Croft, from the Tomb Raider game. White, usually male but occasionally female, digging up the spoils of a vanished culture in colonized lands.

Depictions of archaeologists in popular culture mirror reality. Many scholars have noted the experts institutions recognize as authorities to discuss or represent the past are overwhelmingly white and mostly male. Archaeology has also been a tool colonizing countries use to consolidate and justify their domination. As a new open-access paper in American Antiquity points out, the first doctoral degree in archaeology was not granted to a Black woman until 1980.

First author Ayana Omilade Flewellen, an assistant professor of anthropology at UC Riverside and co-founder of the Society of Black Archaeologists, is working to change this by investigating antiblackness within the discipline, increasing the visibility of Black archaeologists and changing how archaeologists are portrayed in the media, and developing strategies to get more Black students to study archaeology.

"Public-facing avenues for history-making have historically excluded Black and Brown people," Flewellen said. "It has been white, extracting value from and not in dialogue with surrounding communities. How can we be part of history making? How can we get more excluded communities engaged in this work?"

The paper urges archaeologists and history professionals to work closely with people who are grappling with racism in public monuments and institutional names in the wake of last year's uprising following the killing of George Floyd. The authors argue that by working with "broad publics who are actively dictating what should be preserved and what should not the field can begin to redress the harm it has perpetuated."

"The past is messy," Flewellen said. "And archaeologists, we're in the dirt."

The authors assert that professionals of color who deal with history, whether as archaeologists, historians, museum curators, or other heritage experts, are often accused of bias in topics related to slavery, racism, or genocide. Their scholarly or public-facing work is often said to lack objectivity or express excessive emotion. The work of white scholars, writing on the same topics, is considered objective and taken more seriously.

"People question the objectivity of Black scholars but everyone, including white scholars, always has our own biases," Flewellen said. "But embracing these biases by working closely with communities, including Indigenous and Asian, usually excluded from history making allows us to have a more human image of the past."

For example, the authors suggest monuments damaged by protestors could be preserved and displayed alongside exhibits contextualizing the damage as part of a broader history that includes the oppression and struggle for equality of Black, Brown and Indigenous peoples in America. Defacing or destroying monuments could be seen not as an attempt to erase history but rather, as part of an active process of making history.

Recognizing acts of Black resistance against such monuments and other markers of white supremacy makes for a more objective, inclusive, and human telling of history, the authors argue. It also shifts attention from a preoccupation with preservation toward critical examination of the histories scholars choose to see, excavate, and steward.

The paper also addresses the challenges of bringing more Black college students into archaeology, which, in America, is usually housed in anthropology departments.

"Many Black students don't even have access," Flewellen said. "Historically Black colleges and universities don't usually have anthropology majors, and there are financial barriers as well. Field schools, necessary to complete training, are expensive, and because there are so few Black archaeologists, it's also hard for Black students to find mentors."

The authors argue Black archaeology, a specialization shaped by Black Feminist theory focusing on Africa and the African Disapora, can help bring more Black people, especially women, into archaeology and work against racism in the discipline.

"An antiracist archaeology is committed to forging sustainable and nurturing connections among archaeologists of all backgrounds, as well as with communities impacted by archaeological work, community organizers and activists, and those working with smaller historical societies that are also fighting to preserve local histories," the authors write.

The paper emerged from a forum last summer and calls on universities to:

Hire and advance more minority faculty and staff through tenure and promotion and into senior-level roles, respectively.

Make the process of obtaining tenure and merit reviews more transparent.

Admit more minority students and offer more scholarships to help them achieve a degree.

Train faculty and graduate students to integrate antiracist pedagogy in their classes.

Rethink curricula and syllabi to incorporate a greater diversity of voices and perspectives.

Reduce and respond to incidents of macro and microaggressions on campus, such as overtly racist abuse and small everyday insults that make for a hostile environment for students of color.

Hire counseling center staff members who are competent to address the psychological stress of minority students.

Many Mario Kart enthusiasts are familiar with the rush of racing down Rainbow Road, barely squeaking around a corner, and catching a power-up from one of the floating square icons on the screen—or, less ideally, slipping on a banana peel laid by another racer and flying off the side of the road into oblivion. This heated competition between multiple players, who use a variety of game tokens and tools to speed ahead or thwart their competitors, is part of what makes the classic Nintendo racing game that has been around since the early 1990s so appealing.

"It's been fun since I was a kid, it's fun for my kids, in part because anyone can play it," says Andrew Bell, a Boston University College of Arts & Sciences assistant professor of earth and environment. But as a researcher studying economic principles, Bell also sees Mario Kart as much more than just a racing game.

In a recent paper, Bell argues that the principles of Mario Kart—especially the parts of it that make it so addictive and fun for players—can serve as a helpful guide to create more equitable social and economic programs that would better serve farmers in low-resource, rural regions of the developing world. That's because, even when you're doing horribly in Mario Kart—flying off the side of Rainbow Road, for example—the game is designed to keep you in the race.

"Farming is an awful thing to have to do if you don't want to be a farmer," Bell says. "You have to be an entrepreneur, you have to be an agronomist, put in a bunch of labor...and in so many parts of the world people are farmers because their parents are farmers and those are the assets and options they had." This is a common story that Bell has come across many times during research trips to Pakistan, Bangladesh, Cambodia, Malawi, and other countries in southern Africa, and is what largely inspired him to focus his research on policies that could aid in development.

In his new paper, Bell argues that policies that directly provide assistance to farmers in the world's poorest developing regions could help reduce poverty overall, while increasing sustainable and environmentally friendly practices. Bell says the idea is a lot like the way that Mario Kart gives players falling behind in the race the best power-ups, designed to bump them towards the front of the pack and keep them in the race. Meanwhile, faster players in the front don't get these same boosts, and instead typically get weaker powers, such as banana peels to trip up a racer behind them or an ink splat to disrupt the other players' screens. This boosting principle is called "rubber banding," and it's what keeps the game fun and interesting, Bell says, since there is always a chance for you to get ahead.

"And that's exactly what we want to do in development," he says. "And it is really, really difficult to do."

In the video game world, rubber banding is simple, since there are no real-world obstacles. But in the real world, the concept of rubber banding to extend financial resources to agricultural families and communities who need it the most is extremely complicated.

Those opportunities might look like this, Bell says: governments could set up a program so that a third party—such as a hydropower company—would pay farmers to adopt agricultural practices to help prevent erosion, so that the company can build a dam to provide electricity. It is a complicated transaction that has worked under very specific circumstances, Bell says, but systems like this—known as Payments for Ecosystem Services (PES)—have been successful in benefitting both the farmers and the environment. A major challenge is finding private companies that are willing to pay for ecosystem services, and connecting them with farmers who are willing to change their agricultural practices. The good news about rubber banding, though, is that the more people participate in such economic programs, the more other people will join in as well; a concept Bell calls "crowding in," in his analysis.

Bell says the biggest obstacle to overcome in most of the world's developing places is figuring out how to route assistance to people in need in the first place—because, until recently, many of the people were essentially living off the grid.

"It's hard to know who is in the back [of the pack]," Bell says.

But Bell says the ability to reach people in the lowest-resource areas has improved in the last decade or so, largely thanks to the adoption of mobile phones. (In another recent paper, Bell and his collaborators found that smartphones can also play a role in understanding and addressing food insecurity.) Now, mobile devices help local governments and organizations identify people searching for more prosperous livelihoods beyond the challenging practice of agriculture and reach out to those people with economic opportunities.

Bell says further expanding access to mobile devices in poor regions of the world would also allow the gap between the richest and poorest families to be better calculated, and could also help measure the success of newly implemented policies and programs.

"Mario Kart's rubber banding ethos is to target those in the back with the items that best help them to close their gap—their own 'golden mushrooms,'" Bell wrote in the paper, referring to the power-up that gives lagging racers powerful speed bursts. Improving environmental stewardship while alleviating poverty requires that researchers and decision-makers consider from the outset, "within their unique context and challenge at-large, what the golden mushroom might be."

A horse's gut microbiome communicates with its host by sending chemical signals to its cells, which has the effect of helping the horse to extend its energy output, finds a new study published in Frontiers in Molecular Biosciences. This exciting discovery paves the way for dietary supplements that could enhance equine athletic performance.

"We are one of the first to demonstrate that certain types of equine gut bacteria produce chemical signals that communicate with the mitochondria in the horse's cells that regulate and generate energy," says Eric Barrey, author of this study and the Integrative Biology and Equine Genetics team leader at the National Research Institute for Agriculture, Food and Environment, France. "We believe that metabolites - small molecules created by breaking down bigger molecules for food or growth - produced by these bacteria have the effect of delaying low blood sugar and inflammation in the cells, which in turn extends the horse's athletic performance."

Links to disease

Mitochondria, which can be briefly described as the energy provider of cells, have been shown in recent studies to be interdependent with gut bacteria. In fact, many diseases associated with mitochondrial dysfunction in humans, such as Parkinson's and Crohn's have been linked to changes in the gut microbiome in many previous studies.

"Studying horses is a good way to assess the link between gut bacteria and mitochondria, because the level of exercise, and thereby mitochondrial function, performed by a horse during an endurance race is similar to that of a human marathon runner," explains Dr Nuria Mach, first author of this paper, also based at the National Research Institute for Agriculture, Food and Environment, France.

She continues, "For this study we gained permission for veterinary doctors to take blood samples from 20 healthy horses of similar age and performance level, at the start and end of the International Endurance Competition of Fontainebleau, an 8-hour horse race in France. These samples provided information about the chemical signals and expression of specific genes, which is the process by which DNA is converted into instructions for making proteins or other molecules. To understand the composition of the horse's gut bacteria metabolites, we obtained fecal samples at the start of the race."

The researchers found that certain bacteria in the gut were linked to the expression of genes by the mitochondria in the cells. Furthermore, the genes that were expressed, or "turned on", were linked to activities in the cell that helped it to adapt to energetic metabolism.

Evolutionary explanation

"Interestingly, mitochondria have a bacterial origin - it is thought they formed a symbiotic relationship with other components to form the first cell. This may explain why mitochondria have this line of communication with gut bacteria," says Barrey.

Mach concludes, "Improving our understanding of the intercommunication between the horse and the gut microbiome could help enhance their individual performance, as well as the method by which they are trained and dietary composition intake. Manipulating the gut microbiota with probiotic supplements as well as prebiotics, to feed the good bacteria, could be a way for increasing the health and balance of the microbiome and horses, to better sustain endurance exercise."

PISCATAWAY, NJ - Adolescents who frequently see billboard or storefront advertisements for recreational cannabis are more likely to use the drug weekly and to have symptoms of a cannabis use disorder, according to a new study in the Journal of Studies on Alcohol and Drugs.

Despite use being illegal for those below age 21 even in states that have approved recreational marijuana, "legalization may alter the ways that youth use cannabis," write the study authors, led by Pamela J. Trangenstein, Ph.D., M.P.H., of the University of North Carolina at Chapel Hill.

An increasing number of states have legalized or are considering legalizing recreational marijuana, and public concern over the risks of cannabis use has declined in recent years, Trangenstein and colleagues note. However, research continues to find cannabis use associated with negative outcomes. These include neuropsychiatric conditions, automobile crashes and substance use disorders.

And marijuana use among teens may be more problematic than in adults. "As the 2019 Surgeon General's Report warned, cannabinoid receptors are crucial for brain development, which is why cannabis use during adolescence carries special risk," the authors write.

To conduct their research, Trangenstein and colleagues used ads on social media sites and apps to recruit 172 teens, ages 15 to 19, who lived in states with legal recreational marijuana and who had used the drug at least once.

Participants answered questions about their use of marijuana and their exposure to its marketing. The latter included seeing advertisements on billboards and storefronts as well as Instagram and Facebook, if they owned or were likely to buy cannabis-branded merchandise (e.g., hats, sunglasses or t-shirts with cannabis logos or other images) and if they reported having a favorite brand or strain of cannabis or related paraphernalia, such as rolling papers.

Compared with those who never saw billboard or storefront ads, those who said they saw them "most of the time" or "always" had seven times the odds of frequent cannabis use and nearly six times the odds of having symptoms of cannabis use disorder. Having a favorite brand was linked to three times the odds of frequent use and symptoms of cannabis use disorder compared with those who did not have a preferred brand.

Further, those who owned or were likely to own cannabis-branded merchandise had 23 times the odds of frequent use as those who did not own and did not plan to own such merchandise.

Unexpectedly, though, teens who occasionally saw cannabis ads on Instagram were 85% less likely to use marijuana frequently compared with those who never saw such promotions. Those who saw them frequently were 93% less likely to use frequently. To explain these unexpected results, the authors reasoned that the teens could be seeing more user-generated content on Instagram than Facebook. Further, Instagram's image-centric style may not contain the text descriptions that teens need to understand new products.

Trangenstein and colleagues note that, although research into cannabis marketing is in its infancy, studies on alcohol and tobacco advertising indicate that "associations between ads and use may not stop at experimentation--ad exposure may facilitate progression toward problematic use, and their association may even be causal."

As states open up access to recreational marijuana for adults, the researchers say, the collateral effect on youth should not be ignored. "[S]tates and other localities with legalized cannabis should exercise special caution regarding forms of marketing that promote brand identification and engagement with youth," they conclude.

A new clinical trial from King's College London's Institute of Psychiatry, Psychology, & Neuroscience, in collaboration with Oxford University, Oxford Health NHS Foundation Trust, Sussex University, and Sussex Partnership NHS Foundation Trust has established an innovative therapy as an effective means of treating paranoid thoughts in people experiencing psychosis.

In research published in JAMA Psychiatry today, participants of the SlowMo therapy trial had eight face-to-face therapy sessions with support from an interactive web platform and app. The app, designed in collaboration with people experiencing psychosis and the Royal College of Art, is used outside the clinic to help individuals feel safer in daily life.

Paranoia is fuelled by "fast thinking"; a thinking style that is driven by instinct and gut feelings. Slowing down can help. SlowMo starts by supporting people to notice their fast thoughts, visualised as grey, fast-spinning bubbles. People learn to slow down for a moment using tips and personalised safer thoughts.

Professor Philippa Garety, Lead Researcher at SlowMo from King's IoPPN said, "In this trial, we have demonstrated that helping people to slow down their thinking, which is a simple idea, but very difficult to achieve unaided, reduces paranoia in everyday life, and improves quality of life and wellbeing. This has been made possible by devising a brief therapy which uses a powerful combination of therapy sessions and a personalised app. It is at least as effective as longer, more complex psychological treatments for paranoia, which are generally more challenging to deliver and frequently not available in clinical services. The results of this trial have been hugely exciting, and they point a way forwards to harnessing digital technology in the service of developing more effective treatments in the future."

362 people from three NHS Foundation Trusts took part in the trial, with half being provided with SlowMo therapy and their usual care, while the other half continued to receive their usual care. Over the course of six months, patients were measured on a number of outcomes, including their ability to slow down thinking. At the end of the trial, the group who had received SlowMo showed reduced levels of paranoia and worry, no longer meeting the threshold for persecutory beliefs and reported significant improvements to their wellbeing and quality of life.

Sam, who lives with psychosis and took part in the study said, "The focus on fast and slow thinking really helped. The eye catching, helpful bubbles taught me that I can end the cycle of worry, and I do not need to think speedily and start panicking. I have got that now for life. Now all my worries are lessened by SlowMo and I have freedom and peace that I did not have before."
The trial was made possible with funding from the National Institute for Health Research and the Medical Research Council (Efficacy and Mechanism Evaluation). The team now have funding to develop SlowMo so that it can be tested in routine NHS services.

Dr Amy Hardy, Digital Lead at SlowMo from King's IoPPN said "It can be difficult for people to make use of traditional therapies, and we are delighted that the trial showed the SlowMo design overcame common barriers to engagement and effectiveness. It had high rates of use and satisfaction, and worked equally well for a wide range of people. We are now working on developing SlowMo so that this accessible therapy will be widely available in the NHS".

CORVALLIS, Ore. - Eucalyptus, a pest-resistant evergreen valued for its hardy lumber and wellness-promoting oil, can be genetically modified not to reproduce sexually, a key step toward preventing the global tree plantation staple from invading native ecosystems.

Oregon State University's Steve Strauss led an international collaboration that showed the CRISPR Cas9 gene editing technique could be used with nearly 100% efficiency to knock out LEAFY, the master gene behind flower formation.

"The flowers never developed to the point where ovules, pollen or fertile seeds were observed," Strauss said. "And there was no detectable negative effect on tree growth or form. A field study should be the next step to take a more careful look at stability of the vegetative and floral sterility traits, but with physical gene mutation we expect high reliability over the life of the trees."

Findings were published in Plant Biotechnology Journal.

Strauss, Ph.D. student Estefania Elorriaga and research assistant Cathleen Ma teamed up with scientists at the University of Colorado, Beijing Forestry University and the University of Pretoria on the research. The greenhouse study involved a hybrid of two species, Eucalyptus grandis and E. urophylla, that is widely planted in the Southern Hemisphere; there are more than 700 species of eucalyptus, most of them native to Australia.

"Roughly 7% of the world's forests are plantations, and 25% of that plantation area contains nonnative species and hybrids," said Elorriaga, now a postdoctoral researcher at North Carolina State. "Eucalyptus is one of the most widely planted genera of forest trees, particularly the 5.7 million hectares of eucalyptus in Brazil, the 4.5 million hectares in China and 3.9 million hectares in India."

Those plantings, the scientists note, can lead to undesirable mingling with native ecosystems. Thus eliminating those trees' ability to sexually reproduce without affecting other characteristics would be an effective way to greatly reduce the potential for invasive spreading in areas where that is considered an important ecological or economic problem.

"This was the first successful application of CRISPR to solve a commercial problem in forest trees," Elorriaga said. "Research with CRISPR in forest trees to modify different traits is ongoing in many laboratories around the world. Global warming is having large impacts on forests of all kinds, and gene editing may be an important new breeding tool to supplement conventional methods."

Strauss points out that despite the promising findings, trees genetically modified as they were in this research could not legally be planted in Brazil, a nation with some of the largest economic value from eucalyptus tree farming.

"The trait could not be used there due to laws against modifying plant reproduction with recombinant DNA methods," he said. "It would also be disallowed for field research or commercial use under sustainable forest management certification in many parts of the world - something scientists have come together to severely criticize in recent years."

A little more than two years ago, Strauss was part of a coalition of forestry researchers to call for a review of what they see as overly restrictive policies regarding biotech research.

"Hopefully, studies like this one, that show how precise and safe the technology can be in modifying traits, and that help to promote ecological safety, will help to change regulations and certification rules," he said. "Happily, such discussions are well underway in many nations."

Two thirds of New Zealanders believed there were 'silver linings' to the country's Alert Level 4 COVID-19 lockdown imposed in March last year, a University of Otago survey has found.

The researchers were able to question New Zealanders while they were at home, giving a unique insight into their lives during the nationwide lockdown between 25 March and 23 April, widely regarded as one of the strictest imposed anywhere in the world.

One year on from lockdown, the results of their study have been published in the international scientific journal, PLOS ONE.

Participants were asked 'Have you experienced any silver linings, or positive aspects during the COVID-19 Level 4 lockdown' and were able to answer 'yes, for me personally', and/or 'yes for wider society', or no. Of the 2,010 participants who completed the online survey, 64 per cent said they could see a silver lining to lockdown.

Lead researcher Dr Matthew Jenkins says New Zealanders talked about a wide range of positive experiences during lockdown, from pride in the country's response, to having more free time to exercise, take up hobbies, or build relationships with their neighbours.

"Lockdown represented a major flashpoint in people's lives and created an opportunity to stop, take stock and to reflect and connect with others.

"Many people reported that kindness and helping behaviours became more common over this period. They described an 'old fashioned sense of community and caring ... that was not apparent before lockdown'."

Increased flexibility in working from home and reduced time spent commuting was frequently mentioned as one of the silver linings of lockdown, enabling people to spend more time with their families.

"Because of the social distancing measures in place, technology became a major way for people to connect socially and for work via online services such as videoconferencing. One participant reported they 'got to speak with my Dad, who lives overseas, daily' while another joined a global online knitting group to maintain social interactions."

Others reported the pride they felt in the country's response to the pandemic, with one commenting, 'we may be a small country, but we are doing an amazing job'.

"There was an increased sense of national unity, expressed by one participant as '... it's brought New Zealanders together, united in our shared COVID experience'."

Participants also talked about the respite that lockdown offered for the environment, with one observing there was, 'less air pollution and nature (was) having a break from humans destroying it' and another enjoying 'hearing birds sing'.

Dr Jenkins says the research offers a valuable insight into what kinds of support could help people survive and thrive under adverse circumstances.

"Our findings show that in a time of turmoil, unrest and psychological distress, many people nonetheless found silver linings. We also speculate that, despite the impact of the lockdown, many people had their psychological needs for social connectedness and autonomy met, and these were likely to have influenced compliance with lockdown measures.

"Identifying these silver linings will help Governments and mental health practitioners identify the support required to help people survive and thrive during prolonged and stressful events, such as pandemics and lockdowns."

Can a mirror turn an orange into a doughnut? The answer is definitely no in the real (macro) world. But at the nanoscale, a mirror can turn an "orange" shaped pattern into a "doughnut" shaped pattern by overlapping the "orange" with its reflected mirror image.

A team of researchers from the University of Technology Sydney (UTS) has shown for the first time that fluorescent nanoparticles placed near a mirror generate unique patterns that can be used to pinpoint their location.

The researchers attribute this effect to the light emitting nanoparticle's interference with its own mirror image. Using this method they can also detect the size of particles to a resolution of one nanometre - or around 1/80,000th of the diameter of a human hair.

This breakthrough in ultra-sensitive measuring technology, published in Nature Communications, could have many applications including tracking and analysing disease causing viruses and other pathogens.

"When we look in a mirror it doesn't change our physical shape, but that's not the case with emission patterns of nanoparticles," says leading co-author Dr Fan Wang from the UTS Institute for Biomedical Materials and Devices.

"If you put a nanoparticle in front of a mirror, it will change its image by itself, and the image shape reflects the spacing between the particle and the mirror. This is due to the phase difference between the emitter and its image," he says.

The researchers describe this encoding of position information from a particle emission's self-interference as the "SELFI effect". The resulting patterns include Gaussian, doughnut and archery target shapes.

"To the best of our knowledge, the spatial distribution of the spontaneous emission's SELFI from multiple emitters at the nanoscale has not been reported," says leading co-author Professor Dayong Jin.

"This SELFI leads to a fast, high-resolution and anti-drift sensing method to accurately resolve the position of a single nanoparticles."

The nanoparticles are doped with many rare-earth element ions to achieve the necessary luminescence to create an effective SELFI.

The authors note this new method is suitable for conventional widefield fluorescence microscopy setups without requiring system modification.

Areas with a relatively greater amount of misogynistic tweets have higher incidences of domestic and family violence, a UNSW study has found.

The study, published in Psychological Science, not only found this connection with domestic and family violence carried over from one year to the next, but also occurred despite the 'usual suspects' of domestic violence, such as alcohol and inequality.

Examples of misogynistic tweets identified by the researchers included, "Women are all bitches," "Whore had it coming," and, "Make me a sandwich, slut."

"We found that misogynistic social media may not be harmless," Professor Tom Denson from UNSW's School of Psychology said.

"It contributes to norms of violence toward women and a hostile worldview that may slip into real-world violence.

"I imagine a lot of people are fairly flippant about what is posted on social media.

"This study suggests caution about posting misogynistic hate speech as even if the person who posts is not violent, such posts seem to create an atmosphere where violence toward women may be more likely."

The UNSW study is the first to use big data to predict domestic violence from misogynistic tweets across a two-year period.

"There is a growing interest in using big data to help address social problems such as criminality," Prof. Denson said.

The research team compiled all of the data reported by local law enforcement agencies in the US to the Federal Bureau of Investigation on arrests for domestic and family violence during a two-year period (2013 - 2014).

They also collected data on a number of population-level characteristics that are known to influence domestic and family violence, such as the availability of alcohol, income inequality, gender inequality, and population size.

"We then collected Twitter data from 2013-2014," Prof. Denson said.

"Twitter makes a randomly selected 1% of their tweets publicly available.

"We coded those tweets for misogynistic content using automated methods and used a geolocation algorithm to locate the origin of the tweets, which we were able to do with a pretty high degree of spatial specificity based on US Census Bureau defined areas."

The researchers ended up with tweets from 827 areas in 47 American states.

"We then combined the data sets and used the number of misogynistic tweets in each area to examine the relationship between misogynistic tweets and domestic and family violence arrests, while controlling for things like alcohol availability, population, and inequality."

The research is part of a growing number of studies examining the extent to which social media can be used to learn more about criminal offending, co-author and PhD candidate at UNSW School of Psychology, Siobhan O'Dean said.

"Other studies have used social media to predict theft, public disorder during right-wing events, and violence and arrests during the 2015 Black Lives Matter protests," Ms O'Dean said.

"Our research contributes to this imperative by finding out how social media can help determine where domestic and family violence is likely to occur.

"That information could be useful for not only law enforcement but also public health interventions which may intervene to counteract norms of misogynistic violence."

The researchers said future research using big data could examine the relationship between misogynistic social media directed toward proponents of the MeToo movement and Women's Marches with subsequent decreases or increases in violence against women.

Sweden's acclaimed research on uterine transplants has taken a new step forward: into the field of health economics. Now, for the first time, there is a scientifically based estimate of how much implementing the treatment costs.

The current research is based on the nine uterine transplants from living donors carried out in 2013, under the leadership of Mats Brännström, Professor of Obstetrics and Gynecology at Sahlgrenska Academy, University of Gothenburg, and Chief Physician at Sahlgrenska University Hospital.

The transplants were performed within the scope of the world's first systematic, scientifically based study in the field. After the first birth in Gothenburg in 2014, there were a further seven births before a woman outside Sweden had a baby after a uterine transplant.

Now that the survey of costs is complete, the results have been reported with certain reservations. First, the number of cases studied is restricted to nine; second, the treatment has taken place as part of a research project, subject to the requirements this has entailed. Nonetheless, the study represents an initial indication of costs.

The researchers arrived at a total average sum per transplant, now reported in the journal Human Reproduction, of EUR 74,564 in current monetary value. This figure comprises costs relating to the recipient and donor alike.

The total includes, first, screening examinations and treatments, such as in vitro fertilization (IVF), in the year preceding the transplant; second, the actual operations on the donor and recipient; and third, costs in the two months after the transplant, including sick leave.

Sick leave (25.7%) was the single largest item in the cost calculation. The other categories were postoperative inpatient care (17.8%), surgery (17.1%), preoperative examinations (15.7%), anesthesia (9.7%), medication (7.8%), postoperative testing (4.0%), and readmission to hospital (2.2%).

The total is described as relatively high, due partly to the extensive scientific requirements. In a future clinical setting, the researchers say, aggregate transplant costs would likely be lower.

Thomas Davidson, Associate Professor in the area of Health Economics and Health Technology Assessment at Linköping University, and first author of the study, puts the matter in perspective.

"In terms of priorities, this study is important because it contributes key data for deciding whether to offer uterine transplants within publicly funded health care. A cost estimate is the starting point for upcoming assessment of whether the intervention is cost-effective."

Cost-effectiveness is usually measured in terms of cost per quality-adjusted life year (QALY) gained -- a yardstick that combines economic aspects with longevity and quality of life.

"In assessing cost-effectiveness, we have to relate both costs and effects, preferably measured in QALYs, to those of alternative treatments," Davidson says.

Lars Sandman -- Professor of Health Care Ethics, head of the Centre for Priority Setting in Health Care at Linköping University, and the study's co-author -- adds his comments.

"There are still essential issues we want to keep investigating. One is how we should regard the effects of a uterine transplant. Should the QALY gain generated include only the benefit to the mother of getting pregnant, giving birth and being the child's parent? Or should the benefit of a child being born and living on for a number of years, adding QALYs, be included as well? It makes a big difference in terms of the cost-effectiveness of the intervention, which is an important factor in the priority-setting context."

Professor Mats Brännström, corresponding author, sums up.

"All the costs of investigation, staff, and hospital care were funded through research grants. The grand total is close to what we'd calculated, and comparable to the current cost of kidney transplantation from a living donor. In all probability, future uterine transplantation will be more cost-effective thanks to the robot-assisted surgical technique we've developed, which means shorter hospital stays and patients returning to work sooner."

Tsukuba, Japan - Dermatomyositis is an idiopathic inflammatory myopathy that has been regarded as an autoimmunity-based disorder, although its pathogenesis remains unclear. In this study, researchers from the University of Tsukuba used a mouse model to identify a mechanism by which dermatomyositis may develop in humans. The animal model and findings can be used to better understand the disease and develop disease-specific treatments.

Dermatomyositis belongs to a group of idiopathic inflammatory myopathies that are associated with the presence of specific autoantibodies in patient sera. Multiple myositis-specific autoantibodies, which target proteins ubiquitously expressed in the nucleus or cytoplasm, have been described. One of these autoantibodies is specific for transcriptional intermediary factor 1γ (TIF1γ).

"Autoimmune diseases constitute a difficult challenge for patients and doctors," says lead author of the study, Professor Naoko Okiyama. "Not only are the diagnosis and treatment of autoimmune diseases clinically difficult, but it is often unclear why and how the diseases developed. In this study, we investigated the role of a specific autoantibody present in the sera of patients with dermatomyositis, the anti-TIF1γ antibody, in the pathogenesis of the disease."

To achieve their goal, the researchers injected TIF1γ protein into normal mice, as well as several mouse models lacking proteins that play distinct roles in the body's immune response. The researchers' aim was to determine which part of the immune system contributes to the development of dermatomyositis. In normal mice, injection of TIF1γ resulted in the production of TIF1γ-specific T cells and anti-TIF1γ autoantibodies, thereby inducing myositis. In this myositis, CD8+ T cell infiltration into muscle cells resulted in muscle fiber wasting. Generally, CD8+ T cells are important for eliminating infected cells, cancer cells, and other damaged cells.

Importantly, the disease severity was significantly reduced when TIF1γ was injected into mice that lacked the ability to present antigens to CD8+ T cells. Adoptive transfer of CD8+ T cells, but not antibodies, collected from TIF1γ-treated mice led to myositis in recipient mice. This suggests that autoreactive CD8+ T cells against TIF1γ contribute to the pathogenesis of dermatomyositis, while autoantibodies against TIF1γ are simply non-pathogenic clinical diagnostic markers.

"In contrast to existing animal models of experimental myositis, which use muscle-specific antigens, our results show that autoreactive T cell-mediated autoimmunity to TIF1γ may play a causal role in dermatomyositis. This new experimental model may be a new tool to further investigate the disease and develop new therapeutics against dermatomyositis," says Professor Okiyama.

The landscape of sloping vineyards on the banks of the River Mosel in Germany is a characteristic symbol of a region, which cannot be understood without its wine: the Mosel wine region. Tourists from all over the world, especially from the neighbouring countries of Belgium, Luxembourg, and The Netherlands visit the area in search of mountains and wine. However, the lack of new generations and the increase in temperatures and short heavy summer rainfall events caused by climate change endanger the production of wine.

In this sense, the European H2020 Diverfarming Project began in 2018 the diversification of a steep-slope, very stony (up to 70%) ecological vineyard. In the majority of the vineyards, the introduction of herbaceous species for plant cover has become widespread, with herbaceous plants in the alleys between the grapevines, but beneath them, it is combated with herbicides or mechanically. With the aim of reducing soil erosion, increasing soil fertility, and mitigating the effects of greenhouse-gas emissions, a team of researchers from the Trier University (Germany) coordinated by Professor Manuel Seeger and Professor Sören Thiele-Bruhn put into practice the introduction of aromatic plants (thyme and oregano) beneath the grapevines of the 'Weingut Dr. Frey' wine-making company.

After three years of diversification the team formed by the researchers Felix Dittrich, Thomas Iserloh, Roman Hüppi, Sophie Ogan, Sören Thiele-Bruhn, Manuel Seeger, and the winemaking entrepreneur Cord Treseler have published the first results of the diversification on the productivity of the grapevines and the quality of the wine. These results show the potential possibilities that these practices have since they have not generated negative effects in the wine production.

Although a certain amount of competition was observed between the aromatic cover and the grapevines for water and nutrients, these effects far from being negative, give rise to thinking that they may have a positive effect on the quality of the wine, as the researcher Manuel Seeger comments. This is related to the reduction of certain nutrients: while the availability of nitrate had no change in the crop diversification, the ammonium, phosphorus, and potassium levels did decrease in the uppermost area of the soil (the first 10 cm). However, it is known that there is a certain relationship between available potassium and wine quality. The results of this study point out that a change in the availability of the mineral acidity of the soil would seem to generate an increase in the quality of these wines. Moreover, the principle of yield compensation was observed: although the yield of the grapevine is slightly lower, this is compensated by an increase in quality.

The study highlights the extreme events at climate level that have taken place over the three years of the diversification. In 2018, storms produced one month's volume of rainfall in the zone in just one hour; whilst in 2019 and 2020 there were record high temperatures and drought. In this way, it is clear that the availability of water and the climate conditions are the most determining factor for the productivity of the vineyard. Despite that being the case, if we take the extreme conditions into account, the diversification has had no negative effects on the yield of the crop or on the quality of the wine. In standardised situations and with the long-term stabilisation of the diversification this opens the door to an increase in profits thanks to the diversification.

The conservation of the characteristic landscape of the zone, the reduction in contaminant emissions, and the increase in biodiversity both in the soil as well as in other organisms such as insects will contribute added value to this sector, which is currently open to changes that enable it to face this lack of a generational substitution and the scenarios which the effects of climate change are expected to bring. All of this is to save the future of the Mosel wine.

The way we move says a lot about the state of our brain. While normal motor behaviour points to a healthy brain function, deviations can indicate impairments owing to neurological diseases. The observation and evaluation of movement patterns is therefore part of basic research, and is likewise one of the most important instruments for non-invasive diagnostics in clinical applications. Under the leadership of computer scientist Prof. Dr Björn Ommer and in collaboration with researchers from Switzerland, a new computer-based approach in this context has been developed at Heidelberg University. As studies inter alia with human test persons have shown, this approach enables the fully automatic recognition of motor impairments and, through their analysis, provides information about the type of the underlying diseases with the aid of artificial intelligence.

For the computer-supported movement analysis, subjects usually have to be tagged with reflective markings or virtual markers have to be applied to the video material produced in the framework of the assessment. Both procedures are comparatively complicated. Furthermore, conspicuous movement behaviour has to be known in advance so that it can be further examined. "A real diagnostic tool should not only confirm motor disorders but be able to recognise them in the first place and classify them correctly," explains Prof. Ommer, who heads the Computer Vision group at the Interdisciplinary Center for Scientific Computing at Heidelberg University.

Precisely that is made possible by the novel diagnostic method developed by his team, and known as "unsupervised behaviour analysis and magnification using deep learning" (uBAM). The underlying algorithm is based on machine learning using artificial neural networks and it recognises independently and fully automatically characteristic behaviour and pathological deviations, as the Heidelberg scientist explains. The algorithm determines what body part is affected and functions as a kind of magnifying glass for behavioural patterns by highlighting different types of deviation directly in the video and making them visible. As part of this, the relevant video material is compared with other healthy or likewise impaired subjects. Progress in treating motor disorders can also be documented and analysed in this way. According to Prof. Ommer, conclusions can also be drawn about the neuronal activity in the brain.

The basis for the uBAM interface is a so-called convolutional neural network, a type of neural network that is used for image recognition and image processing purposes especially. The scientists trained the network to identify similar movement behaviour in the case of different subjects, even in spite of great differences in their outward appearance. That is possible because the artificial intelligence can distinguish between posture and appearance. Besides the recognition and quantification of impairments, a detailed analysis of the symptoms is also important. "To study them in detail, we use a generative neural network," says Prof. Ommer. "That way we can help neuroscientists and clinicians focus on subtle deviations in motor behaviour that are likely to be overlooked with the naked eye, and make them easily visible by magnifying the deviation. Then we can exactly demarcate the type of disease in the individual case."

The research team has already been able to prove the effectiveness of this new approach with the aid of different animal models and studies with human patients. They tested, inter alia, the precision with which uBAM can differentiate between healthy and impaired motor activity. In their publication on the topic, the scientists report a very high retrieval rate both in mice and human patients. "In all, our study shows that, as compared to conventional methods, the approach based on artificial intelligence delivers more detailed results with significantly less effort," Björn Ommer emphasises.

With respect to the application, the scientists hope that uBAM will be used both in basic biomedical research and in clinical diagnostics and beyond. Prof. Ommer: "The interface can be applied where traditional methods prove too complicated, tedious, or not efficient enough. Potentially it could lead to a better understanding of neuronal processes in the brain and the development of new therapeutic options."

Besides the Heidelberg researchers working with Prof. Ommer, scientists from the University of Zurich and University Hospital Zurich, Balgrist University Hospital and the Neuroscience Center Zurich were also involved in developing the uBAM interface. Part of the funding for the study came from the German Research Foundation as well as the Branco Weiss Fellowship Society in Science and the Swiss National Foundation. The results were published in the journal "Nature Machine Intelligence".